self tolerance

Summary

Summary: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.

Top Publications

  1. ncbi Control of regulatory T cell development by the transcription factor Foxp3
    Shohei Hori
    Laboratory of Immunopathology, Research Center for Allergy and Immunology, Institute for Physical and Chemical Research, Yokohama 230 0045, Japan
    Science 299:1057-61. 2003
  2. ncbi Regulatory T cells exert checks and balances on self tolerance and autoimmunity
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Nat Immunol 11:7-13. 2010
  3. ncbi Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases
    S Sakaguchi
    Precursory Research for Embryonic Science and Technology PRESTO, Research and Development Corporation of Japan JRDC, Tsukuba Life Science Center
    J Immunol 155:1151-64. 1995
  4. ncbi Projection of an immunological self shadow within the thymus by the aire protein
    Mark S Anderson
    Section on Immunology and Immunogenetics, Joslin Diabetes Center Department of Medicine, Brigham and Women s Hospital Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Science 298:1395-401. 2002
  5. ncbi Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Annu Rev Immunol 22:531-62. 2004
  6. ncbi Antigen presentation in the thymus for positive selection and central tolerance induction
    Ludger Klein
    Institute for Immunology, Ludwig Maximilians University, Goethestrasse 31, 80336 Munich, Germany
    Nat Rev Immunol 9:833-44. 2009
  7. pmc Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity
    Emilie Mamessier
    Centre de Recherche en Cancerologie de Marseille, INSERM UMR U891, Marseille, France
    J Clin Invest 121:3609-22. 2011
  8. ncbi Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells
    Chandrashekhar Pasare
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 299:1033-6. 2003
  9. ncbi Regulatory T cell lineage specification by the forkhead transcription factor foxp3
    Jason D Fontenot
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Immunity 22:329-41. 2005
  10. ncbi Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide
    M S Jordan
    The Wistar Institute, Philadelphia, PA 19104, USA
    Nat Immunol 2:301-6. 2001

Detail Information

Publications273 found, 100 shown here

  1. ncbi Control of regulatory T cell development by the transcription factor Foxp3
    Shohei Hori
    Laboratory of Immunopathology, Research Center for Allergy and Immunology, Institute for Physical and Chemical Research, Yokohama 230 0045, Japan
    Science 299:1057-61. 2003
    ..Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells...
  2. ncbi Regulatory T cells exert checks and balances on self tolerance and autoimmunity
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Nat Immunol 11:7-13. 2010
    Immunological self tolerance is maintained at least in part by regulatory T (T(reg)) cells that actively and dominantly control potentially hazardous self-reactive T cells in the periphery...
  3. ncbi Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases
    S Sakaguchi
    Precursory Research for Embryonic Science and Technology PRESTO, Research and Development Corporation of Japan JRDC, Tsukuba Life Science Center
    J Immunol 155:1151-64. 1995
    ..Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases...
  4. ncbi Projection of an immunological self shadow within the thymus by the aire protein
    Mark S Anderson
    Section on Immunology and Immunogenetics, Joslin Diabetes Center Department of Medicine, Brigham and Women s Hospital Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
    Science 298:1395-401. 2002
    ..These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity...
  5. ncbi Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Annu Rev Immunol 22:531-62. 2004
    ....
  6. ncbi Antigen presentation in the thymus for positive selection and central tolerance induction
    Ludger Klein
    Institute for Immunology, Ludwig Maximilians University, Goethestrasse 31, 80336 Munich, Germany
    Nat Rev Immunol 9:833-44. 2009
    Understanding how thymic selection imparts self-peptide-MHC complex restriction and a high degree of self tolerance on the T cell repertoire requires a detailed description of the parameters that shape the MHC ligand repertoire of ..
  7. pmc Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity
    Emilie Mamessier
    Centre de Recherche en Cancerologie de Marseille, INSERM UMR U891, Marseille, France
    J Clin Invest 121:3609-22. 2011
    ..This highlights the importance of developing future therapies able to restore NK cell cytotoxicity to limit/prevent tumor escape from antitumor immunity...
  8. ncbi Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells
    Chandrashekhar Pasare
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 299:1033-6. 2003
    ..This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products...
  9. ncbi Regulatory T cell lineage specification by the forkhead transcription factor foxp3
    Jason D Fontenot
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Immunity 22:329-41. 2005
    ..Analysis of Foxp3 expression during thymic development suggests that this mechanism is not hard-wired but is dependent on TCR/MHC ligand interactions...
  10. ncbi Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide
    M S Jordan
    The Wistar Institute, Philadelphia, PA 19104, USA
    Nat Immunol 2:301-6. 2001
    ..Our findings indicate that specificity for self-peptides directs the selection of CD4+CD25+ regulatory thymocytes by a process that is distinct from positive selection and deletion...
  11. pmc Selection of self-reactive T cells in the thymus
    Gretta L Stritesky
    Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Annu Rev Immunol 30:95-114. 2012
    ..We also outline molecular pathways unique to each lineage and consider possible commonalities to their development and survival...
  12. ncbi Missing self recognition and self tolerance of natural killer (NK) cells
    David H Raulet
    Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720 3200, USA
    Semin Immunol 18:145-50. 2006
    ..activity can be modulated independently of inhibitory receptors specific for MHC molecules, and that such modulation may contribute to self tolerance. This review summarizes current understanding of NK cell recognition and self tolerance.
  13. ncbi Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
    Jeong M Kim
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 8:191-7. 2007
    ..We suggest that self-reactive T cells are continuously suppressed by T(reg) cells and that when suppression is relieved, self-reactive T cells become activated and facilitate accelerated maturation of dendritic cells...
  14. ncbi Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self
    J Derbinski
    Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, INF 280, D-69120, Germany
    Nat Immunol 2:1032-9. 2001
    ..However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens...
  15. ncbi Sites and stages of autoreactive B cell activation and regulation
    Mark J Shlomchik
    Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 28:18-28. 2008
    ..Integrating classic work with recent insights, emphasis is placed on efforts to pinpoint the precursor cells for autoantibody-secreting cells and the unique stimuli and pathways by which they are activated...
  16. ncbi NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner
    Fumiko Kajiura
    Department of Molecular and Environmental Pathology, School of Medicine, University of Tokushima, Tokushima, Japan
    J Immunol 172:2067-75. 2004
    ....
  17. ncbi Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes
    A Gonzalez
    Institut de Genetique et de Biologie Moleculaire et Cellulaire CNRS INSERM ULP, Strasbourg, France
    Nat Immunol 2:1117-25. 2001
    ..5 cells, permitting their full activation and attack of pancreatic islets; rather, it tempered the aggressiveness of the insulitic lesion and the extent of beta cell destruction...
  18. ncbi Peripheral tolerance of CD8 T lymphocytes
    William L Redmond
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Immunity 22:275-84. 2005
    ..A second critical factor that defines "self" and drives tolerance through deletion, anergy, or suppression is the persistence of antigen...
  19. ncbi The enemy within: keeping self-reactive T cells at bay in the periphery
    Lucy S K Walker
    Department of Pathology, University of California San Francisco, 94143, USA
    Nat Rev Immunol 2:11-9. 2002
    ..In this review, new developments in our understanding of peripheral tolerance are discussed...
  20. pmc Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity
    Caspar Ohnmacht
    Institute for Immunology, Department of Medicine, University of Munich, 80336 Munich, Germany
    J Exp Med 206:549-59. 2009
    ..This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions...
  21. pmc A two-step process for thymic regulatory T cell development
    Chan Wang Joaquim Lio
    Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 28:100-11. 2008
    ....
  22. pmc Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells
    Matthieu Giraud
    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:535-40. 2012
    ..Thus, transcript mapping and ChIP-seq data indicate that Aire activates ectopic transcription not through specific recognition of PTA gene promoters but by releasing stalled polymerases...
  23. pmc The BH3-only proteins Bim and Puma cooperate to impose deletional tolerance of organ-specific antigens
    Daniel H D Gray
    Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    Immunity 37:451-62. 2012
    ..Our data show that Puma cooperates with Bim to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease...
  24. pmc Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment
    Nathalie T Joncker
    Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA
    J Exp Med 207:2065-72. 2010
    ..These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease...
  25. pmc Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis
    Vissia Viglietta
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 199:971-9. 2004
    ..These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS...
  26. ncbi Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
    Katharina Aschenbrenner
    Research Institute of Molecular Pathology, 1030 Vienna, Austria
    Nat Immunol 8:351-8. 2007
    ..Thus, 'routing' of mTEC-derived self antigens may determine whether specific thymocytes are deleted or enter the regulatory T cell lineage...
  27. ncbi Autophagic compartments gain access to the MHC class II compartments in thymic epithelium
    Michiyuki Kasai
    Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama shi, 4 7 1 Gakuen, Musashimurayama shi, Tokyo 208 0011, Japan
    J Immunol 183:7278-85. 2009
    ..These results strongly suggest that the cytoplasmic self-Ags gain access to the H2-DM-positive compartments via the autophagic process in the thymus...
  28. pmc Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance
    Masashi Yano
    Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
    J Exp Med 205:2827-38. 2008
    ..Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment...
  29. ncbi Impaired responsiveness to T-cell receptor stimulation and defective negative selection of thymocytes in CCR7-deficient mice
    Ana C M Davalos-Misslitz
    Institute of Immunology, Hannover Medical School, Hannover, Germany
    Blood 110:4351-9. 2007
    ....
  30. pmc Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1
    Anthony Meager
    Biotherapeutics, National Institute for Biological Standards and Control, South Mimms, United Kingdom
    PLoS Med 3:e289. 2006
    ....
  31. pmc Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells
    Lars Oliver Tykocinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, D 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 107:19426-31. 2010
    ..Transient gene expression could conceivably add to the local diversity of self-antigen display thus enhancing the efficacy of central tolerance...
  32. ncbi BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes
    Philippe Bouillet
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, P O The Royal Melbourne Hospital, Victoria 3050, Australia
    Nature 415:922-6. 2002
    ..TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection...
  33. ncbi Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation
    B Salomon
    The Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    Annu Rev Immunol 19:225-52. 2001
    ..The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed...
  34. ncbi Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla
    Mitsuru Matsumoto
    Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
    Eur J Immunol 41:12-7. 2011
    ..e. Aire does not play a neutral role in mTEC differentiation. This review discusses when and how Aire plays an important role in controlling the organization of mTECs required for the expression of self-antigen genes...
  35. pmc Failure to censor forbidden clones of CD4 T cells in autoimmune diabetes
    Sylvie Lesage
    Australian Cancer Research Foundation Genetics Lab, Medical Genome Centre, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
    J Exp Med 196:1175-88. 2002
    ....
  36. ncbi Migration rules: functional properties of naive and effector/memory-like regulatory T cell subsets
    J Huehn
    Exp Rheumatology, Charite Universitaetsmedizin Berlin, Campus Mitte, Berlin, Germany
    Curr Top Microbiol Immunol 293:89-114. 2005
    ..Notably, the potential heterogeneity of Tregs with respect to phenotype and function deserves attention and is a major issue discussed in this review...
  37. ncbi Importance of MHC class 1 alpha2 and alpha3 domains in the recognition of self and non-self MHC molecules
    M H Newberg
    Department of Microbiology, University of Virginia, Charlottsville, 22908, USA
    J Immunol 156:2473-80. 1996
    ....
  38. ncbi Human regulatory T cells and their role in autoimmune disease
    Clare Baecher-Allan
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Immunol Rev 212:203-16. 2006
    ..In this review, we discuss human natural regulatory T cells, what is known about their function, and their associations with specific autoimmune diseases...
  39. ncbi Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo
    Marc A Gavin
    Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA
    Nat Immunol 3:33-41. 2002
    ..DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in T(S) cells, as well as several anti-apoptotic genes that may mediate their survival...
  40. ncbi Gld and lpr mice: single gene mutant models for failed self tolerance
    A Bhandoola
    Department of Pathology, University of Pennsylvania Medical School, Philadelphia
    Int Rev Immunol 11:231-44. 1994
    ..The availability of molecular probes to the gene products of lpr and gld should shortly lead to a better understanding of the acquisition of self tolerance during T cell maturation and of autoimmunity.
  41. pmc Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels
    Jens Derbinski
    Division of Developmental Immunology, German Cancer Research Center, D 69120 Heidelberg, Germany
    J Exp Med 202:33-45. 2005
    ..Our data document a remarkable cellular and molecular specialization of the thymic stroma in order to mimic the transcriptome of multiple peripheral tissues and, thus, maximize the scope of central self-tolerance...
  42. ncbi The impact of self-tolerance on the polyclonal CD8+ T cell repertoire
    Helmut W H G Kessels
    Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Immunol 172:2324-31. 2004
    ..Thus, while individual T cells are markedly cross-reactive, the ability to distinguish between closely related Ags is introduced at the polyclonal T cell level...
  43. pmc Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire
    Matthew A Burchill
    Department of Laboratory Medicine and Pathology, Center for Immunology, The Cancer Center, University of Minnesota, 312 Church Street SE, 6 116 Nils Hasselmo Hall, Minneapolis, MN 55455 USA
    Immunity 28:112-21. 2008
    ..Our data support a two-step model of Treg cell differentiation in which TCR and CD28 signals induce cytokine responsiveness and STAT5-inducing cytokines then complete the program of Treg cell differentiation...
  44. ncbi Effects of the lpr mutation on elimination and inactivation of self-reactive B cells
    J C Rathmell
    Program in Immunology, Stanford University School of Medicine, CA 94305
    J Immunol 153:2831-42. 1994
    ..The possible basis for that defect is discussed...
  45. ncbi "Promiscuous" expression of tissue antigens in the thymus: a key to T-cell tolerance and autoimmunity?
    L Klein
    Dana Farber Cancer Institute, Department of Cancer Immunology and AIDS, Boston, MA 02115, USA
    J Mol Med (Berl) 78:483-94. 2000
    ..We summarize recent experimental evidence supporting this novel concept and discuss implications for autoimmunity...
  46. ncbi Natural autoreactive B cells in transgenic mice reproduce an apparent paradox to the clonal tolerance theory
    S Koenig-Marrony
    Laboratoire d'Immunopathologie, , , Strasbourg, France
    J Immunol 166:1463-70. 2001
    ..Thus, these mouse lines reproduce an apparent paradox to the clonal tolerance theory meriting further investigation of the biological significance of this phenomenon...
  47. ncbi Contribution of receptor editing to the antibody repertoire
    R Casellas
    Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 291:1541-4. 2001
    ..These results suggest that receptor editing represents a major force in shaping the antibody repertoire...
  48. pmc Transcriptional regulation by AIRE: molecular mechanisms of central tolerance
    Part Peterson
    Institute of General and Molecular Pathology, University of Tartu, Tartu 5O411, Estonia
    Nat Rev Immunol 8:948-57. 2008
    The negative selection of T cells in the thymus is necessary for the maintenance of self tolerance. Medullary thymic epithelial cells have a key function in this process as they express a large number of tissue-specific self antigens that ..
  49. ncbi Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors
    Chyi Song Hsieh
    Department of Medicine, Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA
    Immunity 21:267-77. 2004
    ..Thus, these data show that a large proportion of naturally arising TR have substantially more efficient interactions with MHC class II bound peptides from the peripheral self than CD25- T cells...
  50. pmc CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease
    Husein Hadeiba
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nat Immunol 9:1253-60. 2008
    ..Our results identify a highly immunosuppressive population of pDCs present in lymphoid tissues...
  51. pmc Deletional tolerance mediated by extrathymic Aire-expressing cells
    James M Gardner
    Diabetes Center, University of California San Francisco UCSF, San Francisco, CA 94122, USA
    Science 321:843-7. 2008
    ..We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection...
  52. ncbi A central role for central tolerance
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    Annu Rev Immunol 24:571-606. 2006
    ....
  53. ncbi Natural versus adaptive regulatory T cells
    Jeffrey A Bluestone
    Diabetes Research Center, University of California, San Francisco, California 94118, USA
    Nat Rev Immunol 3:253-7. 2003
    ..Here, we propose the existence of two subsets of CD4+ T(Reg) cells--natural and adaptive--that differ in terms of their development, specificity, mechanism of action and dependence on T-cell receptor and co-stimulatory signalling...
  54. ncbi Editors and editing of anti-DNA receptors
    H Li
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Immunity 15:947-57. 2001
    ..Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity...
  55. pmc Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease
    Bo Zhu
    Institute of Cell and Molecular Science, Barts and London School of Medicine and Dentistry, University of London, London E1 2AT, England, UK
    J Exp Med 205:2295-307. 2008
    ..These results demonstrate that Egr-2 is an intrinsic regulator of effector T cells and controls the expansion of self-reactive T cells and development of autoimmune disease...
  56. ncbi Regulation of immune responses through inhibitory receptors
    E O Long
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
    Annu Rev Immunol 17:875-904. 1999
    ..Ligands for many of the other receptors have yet to be identified. The inhibitory-receptor superfamily appears to regulate many types of immune responses by blocking cellular activation signals...
  57. ncbi Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self
    Je Wook Lee
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nat Immunol 8:181-90. 2007
    ..Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells...
  58. pmc Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance
    Hye Jung Kim
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 467:328-32. 2010
    ..Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease...
  59. pmc SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling
    Kevin Evel-Kabler
    Center for Cell and Gene Therapy, Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Clin Invest 116:90-100. 2006
    ..DC immunization can activate autoreactive T cells but rarely causes autoimmune pathologies, indicating that self tolerance at the host level is still maintained in the vaccinated hosts...
  60. ncbi Antigens derived from melanocyte differentiation proteins: self-tolerance, autoimmunity, and use for cancer immunotherapy
    Victor H Engelhard
    Carter Immunology Center and Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
    Immunol Rev 188:136-46. 2002
    ..This model also allows the rapid and systematic examination of parameters for the effective use of synthetic peptide vaccines...
  61. pmc Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen
    Haochu Huang
    Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 103:3734-9. 2006
    ..These studies portray, in a single system, the range of tolerance mechanisms applied to potentially pathogenic B cells, and serve as a base for dissecting where T cell help intervenes and where therapeutic agents impinge...
  62. pmc Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters
    Jörn Gotter
    Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    J Exp Med 199:155-66. 2004
    ..These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression...
  63. pmc Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo
    Caroline Sola
    Innate Pharma, 13009 Marseille, France
    Proc Natl Acad Sci U S A 106:12879-84. 2009
    ..Finally, the long-term infusion of anti-KIR mAb neither abolished NK cell education nor tumor cell recognition. Therefore, these results strongly support the use of inhibitory receptor blockade in cancer patients...
  64. pmc Self-tolerance to the murine homologue of a tyrosinase-derived melanoma antigen: implications for tumor immunotherapy
    T A Colella
    Department of Microbiology and the Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA
    J Exp Med 191:1221-32. 2000
    ..The relevance of this model to an understanding of the human immune response to tyrosinase is discussed...
  65. ncbi The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells
    Petter Brodin
    Department of Microbiology, Tumor and Cell Biology, Strategic Research Center for Studies of Integrative Recognition in the Immune System IRIS, Karolinska Institutet, corrected Stockholm, Sweden
    Blood 113:2434-41. 2009
    ..Our data suggest that the capacity of an individual NK cell to respond to stimulation is quantitatively controlled by the extent of inhibitory signals that are received from MHC class I molecules during NK-cell education...
  66. ncbi T cell recognition of a highly conserved epitope in heat shock protein 60: self-tolerance maintained by TCR distinguishing between asparagine and aspartic acid
    Mark S Lillicrap
    Department of Medicine, University of Cambridge, Cambridge CB2 2QQ, UK
    Int Immunol 16:405-14. 2004
    ....
  67. pmc A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules
    Nadine C Fernandez
    Department of Molecular and Cell Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA
    Blood 105:4416-23. 2005
    ..Thus, self-tolerance of NK cells in normal animals can occur independently of MHC-mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK cells, as also proposed for B and T cells...
  68. ncbi Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice
    Noriyuki Kuroda
    Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
    J Immunol 174:1862-70. 2005
    ..With the use of inbred Aire-deficient mouse strains, we also demonstrate the presence of some additional factor(s) that determine the target-organ specificity of the autoimmune disease caused by Aire deficiency...
  69. pmc The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription
    Emily S Venanzi
    Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 105:15860-5. 2008
    ..This variable self may be beneficial in preventing uniform holes in the T-cell repertoire in individuals of a species, but at the cost of variable susceptibility to autoimmunity...
  70. ncbi Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy
    Mario P Colombo
    Fondazione IRCCS Istituto Nazionale Tumori Experimental Oncology, Via G Venezian 1, Milan, 20133 Italy
    Nat Rev Cancer 7:880-7. 2007
    ....
  71. ncbi Regulation of autoreactive antibodies
    Sergey Yurasov
    Molecular Immunology, The Rockefeller University, New York, New York, USA
    Curr Opin Rheumatol 19:421-6. 2007
    ..This review examines current knowledge on the regulation and selection of autoreactive B cells in mouse models, and in healthy humans and patients with autoimmune disorders...
  72. ncbi In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: maintained tolerance to normal cells even in the presence of IL-2
    Gustaf Vahlne
    Department for Microbiology, Tumor and Cell Biology and Strategic Research Center for Studies of Integrative Recognition in the Immune System IRIS, Karolinska Institutet, Stockholm, Sweden
    Eur J Immunol 40:813-23. 2010
    ..c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I-expressing tumors...
  73. ncbi Thymic cortical epithelium induces self tolerance
    Kissinger P Goldman
    Ghost Lab, LCMI, NIAID, NIH, Bethesda, MD, USA
    Eur J Immunol 35:709-17. 2005
    ..These results establish the ability of cortical epithelium to induce central tolerance, and impinge on several of the models concerning positive selection of newly developing T cells...
  74. ncbi Self-antigen presentation by thymic stromal cells: a subtle division of labor
    L Klein
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Curr Opin Immunol 12:179-86. 2000
    ....
  75. ncbi Peripheral-antigen-expressing cells in thymic medulla: factors in self-tolerance and autoimmunity
    D Hanahan
    Department of Biochemistry and Biophysics Hormone Research Institute University of California at San Francisco CA 94143 0534 USA
    Curr Opin Immunol 10:656-62. 1998
    ..Thymus transplantation demonstrates a functional capability of such expression for self-tolerance induction. Correlative studies suggest that impaired thymic expression confers susceptibility to autoimmune disease...
  76. ncbi Defective central tolerance induction in NOD mice: genomics and genetics
    Silvia Zucchelli
    Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
    Immunity 22:385-96. 2005
    ..Intersection of the data from the two approaches points to a small set of attractive candidate genes...
  77. pmc Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs
    A Pugliese
    Immunogenetics Program, Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida, USA
    J Clin Invest 107:555-64. 2001
    ....
  78. pmc Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice
    K Salojin
    Autoimmunity Diabetes Group, The John P Robarts Research Institute, London, Ontario, Canada N6G 2V4
    J Exp Med 186:887-97. 1997
    ..These findings implicate mSOS as an important mediator of downregulation of Ras signaling in hyporesponsive NOD T cells...
  79. pmc Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation
    Junli Yu
    Immunology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Blood 113:3875-84. 2009
    ....
  80. ncbi Self-tolerance of natural killer cells
    David H Raulet
    Department of Molecular and Cell Biology, Cancer Research Laboratory, 485 Life Science Addition, University of California, Berkeley, California 94720, USA
    Nat Rev Immunol 6:520-31. 2006
    ..Recent studies have produced important new information about NK-cell self-tolerance. Here, we review the evidence for and against possible mechanisms of NK-cell self-tolerance, with an emphasis on the role of MHC-specific receptors...
  81. ncbi Altered selection processes of B lymphocytes in autoimmune NZB/W mice, despite intact central tolerance against DNA
    U Wellmann
    Division of Molecular Immunology, Department of Medicine III, , Erlangen, Germany
    Eur J Immunol 31:2800-10. 2001
    ..We propose different B cell receptor signaling thresholds for the NZB/W compared to C57BL/6 B cells. This could explain the quantitative differences in the B cell repertoire as well as the hyperactivity of B cells from NZB/W mice...
  82. ncbi Re-establishing peripheral tolerance in the absence of CTLA-4: complementation by wild-type T cells points to an indirect role for CTLA-4
    Elizabeth A Tivol
    Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee WI 53201, USA
    J Immunol 169:1852-8. 2002
    ..In addition, a rapid reduction in the ratio of CTLA-4-deficient to wild-type cells was observed. We propose two possible indirect mechanisms by which CTLA-4 may function in the establishment and maintenance of peripheral tolerance...
  83. ncbi Dendritic cell apoptosis in the maintenance of immune tolerance
    Min Chen
    Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 311:1160-4. 2006
    ..The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance...
  84. pmc Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells
    Nathalie T Joncker
    Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720 3200, USA
    Immunol Rev 224:85-97. 2008
    ....
  85. ncbi The innate immune response to tumors and its role in the induction of T-cell immunity
    Andreas Diefenbach
    Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA
    Immunol Rev 188:9-21. 2002
    ..The recognition of induced-self ligands as a strategy to recognize abnormal self sets a precedent for a new immune recognition strategy of the innate immune system...
  86. pmc Contrasting models of promiscuous gene expression by thymic epithelium
    Geoffrey O Gillard
    Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA
    J Exp Med 202:15-9. 2005
    ..However, as discussed here, an alternative model-whereby TRA expression is regulated by conserved developmental programs active in developing mTECs-may be equally plausible...
  87. ncbi Persistence of physiological self antigen is required for the regulation of self tolerance
    K M Garza
    Departments of Microbiology and Pathology, University of Virginia, Charlottesville, VA 22908, USA
    J Immunol 164:3982-9. 2000
    ..In contrast, exposure to endogenous ovarian Ag confined to the neonatal period is insufficient for the induction and maintenance of tolerance to ZP3...
  88. ncbi Macrophage pattern recognition receptors in immunity, homeostasis and self tolerance
    Subhankar Mukhopadhyay
    Sir William Dunn School of Pathology, Oxford, UK
    Adv Exp Med Biol 653:1-14. 2009
    ..In the light of present knowledge ofmacrophage surface antigens, we discuss self versus nonself recognition, microbicidal effector functions and self tolerance in the innate immune system.
  89. ncbi Transcriptional regulation in thymic epithelial cells for the establishment of self tolerance
    Mitsuru Matsumoto
    Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
    Arch Immunol Ther Exp (Warsz) 55:27-34. 2007
    Thymic epithelial cells (TECs) play pivotal roles in the establishment of self tolerance through critical dialogue with developing thymocytes...
  90. ncbi Central tolerance: good but imperfect
    Alena M Gallegos
    Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 7370, USA
    Immunol Rev 209:290-6. 2006
    ..In addition, we recently investigated the efficiency of central tolerance to TSA during ontogeny, and we report that this process was less efficient in neonates than adult animals...
  91. ncbi Licensing of natural killer cells by self-major histocompatibility complex class I
    Wayne M Yokoyama
    Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunol Rev 214:143-54. 2006
    ....
  92. ncbi Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T cells
    Kamalesh K Bala
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Howard Hall 323C, 660 W Redwood St, Baltimore, MD 21201, USA
    Arch Immunol Ther Exp (Warsz) 54:307-21. 2006
    ..In vitro expansion of antigen-specific CD4(+)CD25(+) T cells and their adoptive transfer into patients suffering from autoimmunity is emerging as a promising new therapeutic approach for these debilitating disorders...
  93. pmc Autoreactive marginal zone B cells are spontaneously activated but lymph node B cells require T cell help
    Laura Mandik-Nayak
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Exp Med 203:1985-98. 2006
    ..Therefore, our study of low affinity autoreactive B cells reveals two distinct but potentially concurrent mechanisms for their activation, of which one is T cell dependent and the other is T cell independent...
  94. ncbi The Le Douarin phenomenon: a shift in the paradigm of developmental self-tolerance
    Antonio Coutinho
    Laboratoire Européen Associé au CNRS, Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Int J Dev Biol 49:131-6. 2005
    ....
  95. ncbi Intact B cell tolerance in the absence of the first component of the classical complement pathway
    A J Cutler
    Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, GB, UK
    Eur J Immunol 31:2087-93. 2001
    A critical role for complement in the regulation of self tolerance has been proposed to explain the strong association between complement deficiency and autoimmunity...
  96. ncbi Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity
    S Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin Kawaharacho 53, Sakyo ku, Kyoto 606 8507, Japan
    Microbes Infect 3:911-8. 2001
    T-cell-mediated dominant control of self-reactive T cells is one mechanism for maintaining immunologic self tolerance. It also hampers the generation of immunity to autologous tumor cells...
  97. pmc Hypothetical review: thymic aberrations and type-I interferons; attempts to deduce autoimmunizing mechanisms from unexpected clues in monogenic and paraneoplastic syndromes
    A Meager
    Biotherapeutics, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potter s Bar, Herts, UK
    Clin Exp Immunol 154:141-51. 2008
    ..These ideas raise numerous questions that others may already have the materials to address...
  98. ncbi Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity
    M Murga
    Department of Animal Biology and Genetics, Faculty of Sciences, University of the Basque Country, Bilbao, E 48080, Spain
    Immunity 15:959-70. 2001
    ..Rather than functioning as a transcriptional activator, E2F2 appears to function as a transcriptional repressor of genes required for normal S phase entry, particularly E2F1...
  99. pmc Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice
    Ava J Wu
    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 99:12287-92. 2002
    ..These data suggest that alterations in the number and function of CD4+CD25+ T cells may be one mechanism by which TNF and anti-TNF modulate type I diabetes mellitus in NOD mice...
  100. ncbi Evolution of autoantibody responses via somatic hypermutation outside of germinal centers
    Jacqueline William
    Department of Laboratory Medicine, Section of Immunobiology, Yale University School of Medicine, Box 208035, New Haven, CT 06520 8035, USA
    Science 297:2066-70. 2002
    ..Fas(lpr) mice proliferated and underwent active somatic hypermutation at the T zone-red pulp border rather than in GCs. Our results implicate this region as an important site for hypermutation and the loss of B cell self-tolerance...
  101. ncbi Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model
    Avinash Bhandoola
    Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Immunity 17:425-36. 2002
    ....

Research Grants67

  1. Induction and maintenance of regulatory T cells
    Mitchell Kronenberg; Fiscal Year: 2013
    ..This proposal will study the mechanisms by which the immune responses are properly controlled. Such knowledge will eventually facilitate the design of novel therapeutic approaches for immunological diseases. ..
  2. A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
    Jacques Robert; Fiscal Year: 2013
    ..We are proposing to continue the maintenance and the development of this unique non-mammalian resource facility for biomedical research for the benefit of the whole scientific community. ..
  3. ANIMAL MODELS OF HYPERTHYROIDISM
    Sandra M McLachlan; Fiscal Year: 2012
    ..use a mouse model of Graves'disease to provide insight into the factors involved in the breakdown in "self tolerance" to self proteins that lead to the abnormal autoimmune response to the thyrotropin receptor...
  4. Immunomodulation in melanoma therapy
    NOAH A CRAFT; Fiscal Year: 2012
    ..This proposal is aimed at understanding the relationship between host immunity and self tolerance as it relates to tumor immunotherapy...
  5. Targeting Sirtuin-1 to enhance Foxp3+ regulatory T-cell function
    Ulf Beier; Fiscal Year: 2013
    ..Furthermore, it is important to learn more about the role of Sirtuin-1 in the immune system, as many investigators pursue Sirtuin-1 enhancement (diabetes mellitus, metabolic syndrome), or Sirtuin-1 suppression (certain cancers). ..
  6. Immune Tolerance and Autoimmunity
    Abul K Abbas; Fiscal Year: 2010
    ..The results are not only of biological significance, but will also provide valuable leads for strategies to induce tolerance as a therapeutic modality. ..
  7. GILT and regulation of Treg development in cutaneous autoimmunity
    KAREN TARASZKA HASTINGS; Fiscal Year: 2013
    ..Since the effect of GILT is not limited to the presentation of TRP1 or cutaneous autoantigens, modulation of GILT expression or activity may be a broadly applied therapeutic approach for autoimmune disease. ..
  8. Role of serum amyloid A in interferon-gamma expression and T helper 1 cell differ
    Rong Lucy He; Fiscal Year: 2013
    ....
  9. Real-time Measurement of Self-antigen Recognition by Lymphocytes In Vivo
    ALEX YEE CHEN HUANG; Fiscal Year: 2012
    ..Successful execution of this project will also provide new insights into potential mechanisms underlying the development of autoimmunity, induction of tumor tolerance and maintenance of homeostatic immune responses. ..
  10. Myeloid-derived Suppressor Cells in Autoimmune Arthritis
    Katalin Mikecz; Fiscal Year: 2012
    ..of ABMT is primarily attributed to hematopoietic stem cell-mediated restoration of immune homeostasis and self tolerance through induction of immunosuppressive regulatory T cells (Tregs)...
  11. Development & Characterization of Tyrosinase Epitope Specific TCR Transgenic Mice
    Shikhar Mehrotra; Fiscal Year: 2010
    ..Successful completion of this proposal would provide us information about the feasibility of using this TIL1383i TCR in T cell adoptive immunotherapy protocols. ..
  12. The immunobiology of CD4+ CD25+ T regulatory cells
    Thomas R Malek; Fiscal Year: 2013
    ..Understanding the factors that reverse autoimmunity in the IL-2Rb- deficient model may also provide new information concerning the etiology and potential therapy that may be generally common to several human autoimmune diseases. ..
  13. Effect of alcohol exposure on human Treg induction &CD36HI monocyte biology
    KATHLEEN ELIZABETH JAEGER; Fiscal Year: 2013
    ..Tregs are critical in the human immune system by maintaining self tolerance and immune homeostasis...
  14. Exosome-induced innate and antigen-specific immune responses in Type 1 Diabetes
    Yang D Dai; Fiscal Year: 2013
    ..We will use EXO as a vehicle for activating DC and delivering antigens. We anticipate that EXO can upregulate Slc11a1 function in DC and thus promote induction of the disease-causing Th1 cells. ..
  15. TGF beta-induced apoptosis in B-lymphocytes
    Philip H Howe; Fiscal Year: 2013
    ..deletion of autoreactive B cells that is critical for normal B lymphocyte development and the maintenance of self tolerance. We have investigated the molecular mechanisms by which TGF[unreadable] aids in maintenance of self tolerance ..
  16. IMMUNOMODULATION OF TRANSPLANT REJECTION BY ANTI-CD3 MAB
    Jeffrey A Bluestone; Fiscal Year: 2013
    ....
  17. Somatic Hypermutation in SLE
    Lawrence J Wysocki; Fiscal Year: 2013
    ..Results of this project will provide basic information about the natural history of autoreactive B cells, which is essential if we are to understand, control and prevent systemic autoimmune disease. ..
  18. T Cell Tolerance &Autoimmunity to Nuclear Antigen La
    A Darise Farris; Fiscal Year: 2012
    ..We seek to understand how these elements control CD4+ T cell fate and phenotype under both steady-state and inflammatory conditions so that we can better understand the development of autoimmune disease. ..
  19. Regulation of dendritic cell inflammatory responses
    Jessica A Hamerman; Fiscal Year: 2013
    ..This work will give insights into how to manipulate the immune system to achieve more efficient elimination of pathogens and to prevent the development of systemic autoimmune disease, such as systemic lupus erythematosus. ..
  20. Quality and location of presented Ag as determinants of tumor-specific immunity
    Victor H Engelhard; Fiscal Year: 2012
    ..These models will allow the investigators to also address mechanisms by which these limitations may be overcome. Success of the work may offer insights into improving immunotherapy approaches for treating cancer patients. ..
  21. The Role of EOS in Regulatory T-cell Biology.
    Drew M Pardoll; Fiscal Year: 2013
    ....
  22. Chromatin states encoding fate commitment and plasticity of tolerant CD8 T cells
    Philip D Greenberg; Fiscal Year: 2013
    ....
  23. Interferon Alpha as a Tool for Gene Discovery in Human Lupus
    Timothy B Niewold; Fiscal Year: 2013
    ..Detailed knowledge of the functional genetic factors present in a given patient could be of great utility in individualizing therapy, and may allow for the development of preventive strategies. ..
  24. Comparison of SKG and ZAP-70 YYAA mutant mice in the development of arthritis
    Lih Yun Hsu; Fiscal Year: 2010
    ..In addition, studying how cytokines are organized within a hierarchical regulatory network should help identify important checkpoints that facilitate the progression from autoimmunity to chronic inflammation. ..
  25. Screening for inhibitors of the T cell Tec kinase, ltk
    Joonsoo Kang; Fiscal Year: 2010
    ..This proposal aims to develop a screen for inhibitors of this enzyme, which could be used to prevent the onset of autoimmune processes in susceptible individuals and to treat and cure patients with these diseases. ..
  26. Characterization of microRNA-regulated signaling pathways in mouse SLE
    Marianthi Kiriakidou; Fiscal Year: 2013
    ..B cells is at the center of SLE pathogenesis and leads to increased production of autoantibodies, failure of self tolerance mechanisms and inadequate clearing of immune complexes...
  27. Is Aberrant MO Stimulation Pivotal in Post-Trauma MODS?
    Carol L Miller-Graziano; Fiscal Year: 2012
    ..cells (DC), play key roles in systemic inflammation, induction of specific immunity, and maintenance of self tolerance. Post injury MO differentiation to appropriately activating or dysfunctional DC depends on circulatory ..
  28. Lymphoid signals for stromal growth and organization in the thymus.
    Howard T Petrie; Fiscal Year: 2012
    ..The goals of this project are to perform an in depth analysis of this very poorly understood two-way interplay between lymphocytes and stromal cells in the thymus, and how these processes shape the development of the immune system. ..
  29. Post-transcriptional regulation of the Dendritic Cell transcriptome
    Miriam Merad; Fiscal Year: 2013
    ..DCs are also involved in preventing autoimmunity by maintaining self tolerance. It is now understood that DCs are not a homogeneous population of cells...
  30. Molecular Mechanisms of Protochordate Allorecognition
    Anthony W De Tomaso; Fiscal Year: 2013
    ..Studying the biology underlying self/non-self recognition in a simpler, ancestral organism will provide opportunities and insights not available in other species. ..
  31. Autoimmune biomarker profiling in tauopathy
    Irving E Vega; Fiscal Year: 2013
    ....
  32. A New Anti-CD27 Monoclonal Antibody Adjuvant for Pancreatic Cancer Vaccines
    SARAH JANE SCHLESINGER; Fiscal Year: 2013
    ....
  33. The IRF - type I interferon system in T cell-mediated immune tolerance
    Michael David; Fiscal Year: 2013
    ..The proposed studies will extend our understanding of the contributions of IRFs and type I interferons in the development of Treg cells that are essential in the maintenance of self-tolerance. ..
  34. POLARIZING T CELL RESPONSES IN VIVO WITH DENDRITIC CELLS
    Bali Pulendran; Fiscal Year: 2013
    ..determine the role of ?-catenin activation in intestinal APCs in maintaining the balance between immunity and self tolerance to an intestinal self-antigen...
  35. The Role of B Cell Maturation Antigen in Controlling Tolerance
    CHRISTINE MOREL COQUERY; Fiscal Year: 2013
    ....
  36. Investigating the Role of microRNA Regulation in Dendritic Cell Function
    BRIAN DAVID BROWN; Fiscal Year: 2010
    ..DCs are also involved in preventing autoimmunity by maintaining self tolerance. The critical role of DCs in both immunity and tolerance has made them important therapeutic targets...
  37. Immunomodulation Requirements for Treg Immunotherapy for autoimmune diabetes
    ALLISON LORAYNE BAYER; Fiscal Year: 2013
    ..abstract_text> ..
  38. Zona Pellucida: Immunopathologic Study
    Kenneth S K Tung; Fiscal Year: 2013
    ..Our study will define many Treg functions relevant to many common human diseases such as: pemphigus vulgaris, IC disease (SLE), Sjogren's syndrome, APS1, gastritis, and male and female idiopathic infertility due to gonadal failure. ..
  39. Molecular and Epigenetic Programs Underlying T cell Tolerance to Tumor Antigens
    Andrea Schietinger; Fiscal Year: 2013
    ....
  40. Environmentally-Induced Ocular Surface Inflammation Mimicking Sjogren's Syndrome
    Michael J Stern; Fiscal Year: 2010
    ..We further propose that the severity of this ALKC is worsened by defective self tolerance mechanisms...
  41. Determining the Impact of SREBP on Adaptive Immunity
    Steven J Bensinger; Fiscal Year: 2013
    ..These studies will provide a foundation for better understanding the relationship between lipid metabolism, proliferation and differentiation in rapidly dividing hematopoietic and immune cells. ..
  42. Genetic Determinants of Mucosal Defense to Salmonella Infection
    Kelly D Smith; Fiscal Year: 2010
    The mucosal immune system must simultaneously decipher pathogens from innocuous flora and maintain self tolerance while promoting long-lasting immunity to pathogens...
  43. NK Cell Differentiation from Stem Cells
    Jeffrey S Miller; Fiscal Year: 2010
    ..In order to induce self tolerance and avoid damage to healthy tissues, NK cells are educated by "self" MHC molecules which bind inhibitory NK ..
  44. Deaf1 isoforms control changes in PTA expression in the NOD PLN during T1D pathog
    CHARLES GARRISON FATHMAN; Fiscal Year: 2013
    ....
  45. Autoimmunity and age-related changes in thymic induction of self-tolerance.
    Howard T Petrie; Fiscal Year: 2013
    ..This will also be tested in the proposed project. ..
  46. Treg-Th17 Axis Modulation and Induction of Tumor Immunity with Cryosurgery
    JESSE JAMES VEENSTRA; Fiscal Year: 2013
    ..shift in this axis towards the pro-inflammatory spectrum (Th17 cells) will allow immune effectors to overcome self tolerance and induce long term anti-tumor immunity...
  47. Regulation of conventional versus innate CD8+ T cell development
    Leslie J Berg; Fiscal Year: 2013
    ..This understanding will aid in efforts to regulate and control the immune system to fight infections and eradicate cancer cells. ..
  48. Cell intrinsic immunopathology of Type I diabetes in humanized mice
    NICHOLE MARIE DANZL; Fiscal Year: 2013
    ....
  49. Tolerance mechanisms regulating the complete HER-2/neu CD+8 T cell repertoire
    Elizabeth M Jaffee; Fiscal Year: 2012
    ..Specifically, we will evaluate a number of mechanisms that may differentially regulate low versus high avidity T cells including: regulatory T cells, T cell signaling pathways, and post-transcriptional regulation. ..
  50. Investigating the Role of IL35 in Anti-Tumor Immunity
    Meghan E Turnis; Fiscal Year: 2013
    ..Research on these Aims should yield exciting knowledge that will advance the field and hopefully prove to be therapeutically beneficial. ..
  51. University of Chicago Autoimmunity Center of Excellence
    Marcus R Clark; Fiscal Year: 2013
    ..They arise from failures in self tolerance. Therefore, we propose to establish the University of Chicago Autoimmunity Center of Excellence (UCACE) with ..
  52. Polymeric biomaterial-based microparticle vaccine for amelioration of Type 1 diab
    Jamal S Lewis; Fiscal Year: 2013
    ..Additionally, our strategic collaborations with the Biomedical Engineering Department, College of Medicine and Diabetes Center of Excellence at the University of Florida boost our capability to complete the desired goals. ..
  53. Control of regulatory T cell differentiation and function
    Steven F Ziegler; Fiscal Year: 2010
    ..Thus, a better understanding of the mechanism by which FOXP3 controls Treg function will provide insight into Treg biology, and identify potential targets for manipulation of this important T cell subset. ..
  54. Immunomodulation in melanoma: Toll like receptors and therapeutic vaccines
    NOAH A CRAFT; Fiscal Year: 2010
    ..This proposal is aimed at understanding the relationship between host immunity and self tolerance as it relates to tumor immunotherapy...
  55. Linking Genetic Variation in the PTPN2 Gene to Autoimmune Disease Susceptibility
    Jane Hoyt Buckner; Fiscal Year: 2010
    ..plays a central role in determining both the magnitude of the adaptive immune response and the maintenance of self tolerance. A loss of IL-2 production or expression of its receptor results in autoimmunity...
  56. Regulatory T Cell Function in Ovarian Cancer
    Kirsten B Moysich; Fiscal Year: 2013
    ..Our statistical and genetic analyses will be carried out by a trained genetic epidemiologist. ..
  57. Molecular mechanisms of T cell anergy
    Fernando Macian; Fiscal Year: 2013
    ..use that knowledge to evaluate the specific role of T cell anergy in two different processes: maintenance of self tolerance and tumor-induced immune tolerance;and finally 3...
  58. Epitope sepcificity relates to GAD65-specific regulation of pathogenesis
    Yang D Dai; Fiscal Year: 2010
    ..and self antigens, whose interactions are essential for initiating adaptive immune responses and establishing self tolerance, we hypothesize that the existing differences within the antigen processing machinery between T1 D-susceptible ..
  59. Immune Dysregulation in HIT
    Gowthami M Arepally; Fiscal Year: 2010
    ..It is expected that these studies will lead to insights into strategies that prevent or modulate immune complications from this life-threatening thrombotic disorder. ..
  60. Thymocyte tuning after selection: mechanisms to avoid autoreactivity
    Terri M Laufer; Fiscal Year: 2010
    ..These experiments will define the mechanisms which regulate a critical thymic pathway that the immune system utilizes to avoid autoreactivity. ..
  61. ITK: an emerging target for treatment of T cell-mediated autoimmune disease
    Joonsoo Kang; Fiscal Year: 2013
    ..A better understanding of this mechanism may provide opportunities to prevent the onset of autoimmune processes in susceptible individuals and to treat and cure patients with these diseases. ..
  62. Integrating beta cell antigenic epitopes into DC-based T1D immunotherapy
    Changqing Xia; Fiscal Year: 2010
    ..provided by applicant): Type 1 diabetes (T1D) is a T cell mediated autoimmune disease where the breakdown of self tolerance to islet beta cell antigens leads to immune mediated islet destruction, loss of insulin production and ..
  63. Mixed Chimerism in Haploidentical Non-human Primates
    Bernhard Hering; Fiscal Year: 2006
    ..abstract_text> ..
  64. Immunodeficiency and Autoimmunity
    ABUL ABBAS; Fiscal Year: 2009
    ..This project will provide valuable information about why immune deficiencies are associated with autoimmunity, and may give insights into the general mechanisms of failure of tolerance and development of systemic autoimmunity. ..
  65. EXPRESSION OF TRANSGENIC TCR GENES IN AUTOIMMUNE 1PR/1PR
    JOHN MOUNTZ; Fiscal Year: 1993
    ..of these mice suggest that T cells undergo abnormal maturation during thymic development prior to induction of self tolerance. These results have led to the suggestion that excessive production of immature autoreactive T cells migrate ..
  66. REGULATORY MECHANISMS IN THE IMMUNE SYSTEM
    John Kappler; Fiscal Year: 2007
    ..abstract_text> ..
  67. DEVELOPMENTAL INFLUENCES ON T CELL RECEPTOR EXPRESSION
    Pamela Fink; Fiscal Year: 1993
    ..a skewing of the TCR repertoire due to the imposition of self tolerance, and/or 4...