thymus gland

Summary

Summary: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.

Top Publications

  1. pmc Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells
    Angela M Thornton
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:3433-41. 2010
  2. pmc The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues
    T Lindsten
    Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 6:1389-99. 2000
  3. doi Regulatory T cells and immune tolerance
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Cell 133:775-87. 2008
  4. pmc Aberrant T cell differentiation in the absence of Dicer
    Stefan A Muljo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 202:261-9. 2005
  5. ncbi Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP
    Vassili Soumelis
    DNAX, 901 California Avenue, Palo Alto, CA 94304, USA
    Nat Immunol 3:673-80. 2002
  6. ncbi Development of a human adaptive immune system in cord blood cell-transplanted mice
    Elisabetta Traggiai
    Institute for Research in Biomedicine IRB, Via Vela 6, 6500 Bellinzona, Switzerland
    Science 304:104-7. 2004
  7. 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
  8. ncbi p63 Is essential for the proliferative potential of stem cells in stratified epithelia
    Makoto Senoo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:523-36. 2007
  9. pmc Epigenetic control of the foxp3 locus in regulatory T cells
    Stefan Floess
    Experimentelle Rheumatologie, Charite Universitaetsmedizin Berlin, Berlin, Germany
    PLoS Biol 5:e38. 2007
  10. pmc Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
    Ye Zheng
    Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nature 463:808-12. 2010

Detail Information

Publications390 found, 100 shown here

  1. pmc Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells
    Angela M Thornton
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:3433-41. 2010
    ..Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically...
  2. pmc The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues
    T Lindsten
    Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell 6:1389-99. 2000
    ..Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis...
  3. doi Regulatory T cells and immune tolerance
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Cell 133:775-87. 2008
    ..Recent research reveals the cellular and molecular basis of Treg development and function and implicates dysregulation of Tregs in immunological disease...
  4. pmc Aberrant T cell differentiation in the absence of Dicer
    Stefan A Muljo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 202:261-9. 2005
    ..Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage...
  5. ncbi Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP
    Vassili Soumelis
    DNAX, 901 California Avenue, Palo Alto, CA 94304, USA
    Nat Immunol 3:673-80. 2002
    ..TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation...
  6. ncbi Development of a human adaptive immune system in cord blood cell-transplanted mice
    Elisabetta Traggiai
    Institute for Research in Biomedicine IRB, Via Vela 6, 6500 Bellinzona, Switzerland
    Science 304:104-7. 2004
    ..This provides a valuable model to study development and function of the human adaptive immune system in vivo...
  7. 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...
  8. ncbi p63 Is essential for the proliferative potential of stem cells in stratified epithelia
    Makoto Senoo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:523-36. 2007
    ..Together, these data identify p63 as a key, lineage-specific determinant of the proliferative capacity in stem cells of stratified epithelia...
  9. pmc Epigenetic control of the foxp3 locus in regulatory T cells
    Stefan Floess
    Experimentelle Rheumatologie, Charite Universitaetsmedizin Berlin, Berlin, Germany
    PLoS Biol 5:e38. 2007
    ....
  10. pmc Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
    Ye Zheng
    Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nature 463:808-12. 2010
    ..Together, our studies demonstrate that the composition, size and maintenance of the T(reg) cell population are controlled by Foxp3 CNS elements engaged in response to distinct cell-extrinsic or -intrinsic cues...
  11. ncbi Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients
    Susan R Schwab
    Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0414, USA
    Science 309:1735-9. 2005
    ..We conclude that lymphocyte egress is mediated by S1P gradients that are established by S1P lyase activity and that the lyase may represent a novel immunosuppressant drug target...
  12. ncbi Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling
    Mark A Daniels
    Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
    Nature 444:724-9. 2006
    ....
  13. pmc Immunosenescence of ageing
    A L Gruver
    Duke University Human Vaccine Institute and Department of Pathology, Duke University Medical Center, Durham, NC, USA
    J Pathol 211:144-56. 2007
    ..Chronic involution of the thymus gland is thought to be one of the major contributing factors to loss of immune function with increasing age...
  14. ncbi p53 is required for radiation-induced apoptosis in mouse thymocytes
    S W Lowe
    Department of Biology, Massachusetts, Cambridge 02139
    Nature 362:847-9. 1993
    ..These results demonstrate that p53 is required for radiation-induced cell death in the thymus but is not necessary for all forms of apoptosis...
  15. 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...
  16. pmc The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor
    Aikaterini S Papadopoulou
    VIB, Leuven, Belgium
    Nat Immunol 13:181-7. 2012
    ..In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity...
  17. ncbi Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells
    H J McKenna
    Immunex Corporation, Seattle, WA 98101, USA
    Blood 95:3489-97. 2000
    ..We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes...
  18. doi Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus
    Susan M Schlenner
    Institute for Immunology, University of Ulm, Ulm, Germany
    Immunity 32:426-36. 2010
    ..Thus, lymphoid-restricted progenitors are the major route to T cells, and distinct origins of lymphoid and myeloid lineages represent a fundamental hallmark of hematopoiesis...
  19. pmc Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function
    Christopher J Haines
    Department of Pediatrics and the Immunology Program, Stanford University, Stanford, CA 94305, USA
    J Exp Med 206:275-85. 2009
    ..The ability to identify viable CD4(+) RTEs by PTK7 staining should be useful for monitoring thymic output in both healthy individuals and in patients with genetic or acquired CD4(+) T cell immunodeficiencies...
  20. pmc The transcription factor PLZF directs the effector program of the NKT cell lineage
    Adam K Savage
    Howard Hughes Medical Institute, Committee on Immunology, Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    Immunity 29:391-403. 2008
    ..We suggest that PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development...
  21. pmc Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice
    Paul W Denton
    Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
    PLoS Med 5:e16. 2008
    ..Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection...
  22. pmc Delta-like 4 is indispensable in thymic environment specific for T cell development
    Katsuto Hozumi
    Department of Immunology and Research Center for Embryogenesis and Organogenesis, Tokai University School of Medicine, Isehara 259 1193, Japan
    J Exp Med 205:2507-13. 2008
    ..These results indicate that the thymus-specific environment for determining T cell fate indispensably requires Dll4 expression to induce Notch signaling in the thymic immigrant cells...
  23. pmc Control of regulatory T cell lineage commitment and maintenance
    Steven Z Josefowicz
    Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Immunity 30:616-25. 2009
    ..In this review we discuss Treg cell differentiation and maintenance with a particular emphasis on molecular regulation of Foxp3 expression, arguably a key to mechanistic understanding of biology of regulatory T cells...
  24. ncbi Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity
    Sun Ying
    Department of Asthma, Allergy and Respiratory Science, Guy s, King s and St Thomas GKT School of Medicine, London, United Kingdom
    J Immunol 174:8183-90. 2005
    ..Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors...
  25. ncbi Zoned out: functional mapping of stromal signaling microenvironments in the thymus
    Howard T Petrie
    Scripps Florida Research Institute, Jupiter, Florida 33458, USA
    Annu Rev Immunol 25:649-79. 2007
    ..Summarizing what is known about the signals the thymus delivers to uncommitted progenitors, or to immature T-committed progenitors, to produce functional T cells is the focus of this review...
  26. doi Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance
    Jelena Nedjic
    Research Institute of Molecular Pathology, Doktor Bohr Gasse 7, 1030 Vienna, Austria
    Nature 455:396-400. 2008
    ..In doing so, it contributes to T-cell selection and is essential for the generation of a self-tolerant T-cell repertoire...
  27. doi Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?
    Jochen Huehn
    Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
    Nat Rev Immunol 9:83-9. 2009
    ....
  28. ncbi Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Nat Immunol 6:345-52. 2005
    ..They are therefore a good target for designing ways to induce or abrogate immunological tolerance to self and non-self antigens...
  29. doi Thymic epithelial cells: working class heroes for T cell development and repertoire selection
    Graham Anderson
    MRC Centre for Immune Regulation, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, UK
    Trends Immunol 33:256-63. 2012
    ..Here, we summarise current knowledge on the development and function of the thymic microenvironment, paying particular attention to the cortical and medullary epithelial compartments...
  30. ncbi Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity
    P M Fernandez-Salguero
    Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Toxicol Appl Pharmacol 140:173-9. 1996
    ..The mechanism(s) responsible for these apparently receptor-independent processes remain unclear but may involve novel, alternative pathways for TCDD-induced toxicity...
  31. doi 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
    ..Here, we discuss these new findings in the context of how individual thymic stromal cell types support T cell selection in a cooperative rather than a redundant manner...
  32. doi Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance
    Maria Hinterberger
    Institute for Immunology, Ludwig Maximilians Universitat, Munich, Germany
    Nat Immunol 11:512-9. 2010
    ..Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4(+) T cell tolerance and support an avidity model of T(reg) cell development versus deletion...
  33. pmc Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice
    M K Kennedy
    Immunex Corporation, Seattle, Washington 98101, USA
    J Exp Med 191:771-80. 2000
    ..Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine...
  34. ncbi RAG-1-deficient mice have no mature B and T lymphocytes
    P Mombaerts
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
    Cell 68:869-77. 1992
    ..Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice...
  35. ncbi Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1
    T Nagasawa
    Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, Japan
    Nature 382:635-8. 1996
    ..In addition, the mutants had a cardiac ventricular septal defect. Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development...
  36. ncbi T cell-specific loss of Pten leads to defects in central and peripheral tolerance
    A Suzuki
    Department of Molecular and Cellular Biology, Osaka University, 565 0871, Osaka, Japan
    Immunity 14:523-34. 2001
    ..Peripheral tolerance to SEB is also impaired in Pten(flox/-) mice. PTEN is thus an important regulator of T cell homeostasis and self-tolerance...
  37. ncbi Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
    Mehrdad Matloubian
    Howard Hughes Medical Institute and Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0414, USA
    Nature 427:355-60. 2004
    ..These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs...
  38. pmc T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse
    Amy E Moran
    Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA
    J Exp Med 208:1279-89. 2011
    ..However, although T(reg) cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that T(reg) cell progenitors compete for recognition of rare stimulatory TCR self-ligands...
  39. pmc CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets
    Julie C Ribot
    Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal
    Nat Immunol 10:427-36. 2009
    ..Thus, the cytokine profiles of peripheral gammadelta T cells are predetermined mainly by a mechanism involving CD27...
  40. pmc CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus
    Daniel A Zlotoff
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
    Blood 115:1897-905. 2010
    ..Together our results illustrate the critical role of chemokine receptor signaling in thymic settling and help to clarify the cellular identity of the physiologic thymic settling progenitors...
  41. pmc Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development
    Yu Lei
    Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan
    J Exp Med 208:383-94. 2011
    ..These results indicate that the XCL1-mediated medullary accumulation of tDCs contributes to nT reg cell development and is regulated by Aire...
  42. ncbi Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance
    S Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Immunol Rev 182:18-32. 2001
    ..They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance...
  43. ncbi Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus
    Tom Taghon
    Division of Biology, MC 156 29, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA
    Immunity 24:53-64. 2006
    ..Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing alphabeta and gammadelta T-lineage cells...
  44. 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...
  45. ncbi CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2
    Thomas R Malek
    Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA
    Immunity 17:167-78. 2002
    ..These observations indicate that the essential function of the IL-2/IL-2R system primarily lies at the level of the production of CD4(+)CD25(+) regulatory T cells...
  46. ncbi The influence of age on T cell generation and TCR diversity
    Keith Naylor
    Department of Medicine, Mayo Clinic and Graduate School, Rochester, MN 55905, USA
    J Immunol 174:7446-52. 2005
    ..The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment...
  47. pmc A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self
    Hyang Mi Lee
    Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 37:475-86. 2012
    ..Thus, these data suggest that the broad range of self-reactivity that elicits thymic Treg cell generation is tuned to secure peripheral tolerance to self...
  48. ncbi Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development
    Ichiro Taniuchi
    Howard Hughes Medical Institute, Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 111:621-33. 2002
    ..Runx3-deficient cytotoxic T cells, but not helper cells, have defective responses to antigen, suggesting that Runx proteins have critical functions in lineage specification and homeostasis of CD8-lineage T lymphocytes...
  49. doi Differential processing of self-antigens by subsets of thymic stromal cells
    Sylvie Guerder
    Centre de Physiopathologie de Toulouse Purpan, Universite Toulouse III Paul Sabatier, Toulouse F 31300, France
    Curr Opin Immunol 24:99-104. 2012
    ..Here, we discuss how these different features allow for the development of a highly diverse but poorly self-reactive repertoire of functional T cells...
  50. doi Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?
    Maria A Curotto de Lafaille
    Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Immunity 30:626-35. 2009
    ....
  51. pmc Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment
    Ute Koch
    Ecole Polytechnique Federale de Lausanne, Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland
    J Exp Med 205:2515-23. 2008
    ..Moreover, they strongly suggest that N1-expressing thymic progenitors interact with DL4-expressing TECs to suppress B lineage potential and to induce the first steps of intrathymic T cell development...
  52. ncbi The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing
    W Jiang
    Laboratory of Molecular Immunology, Rockefeller University, New York, New York 10021, USA
    Nature 375:151-5. 1995
    ..Thus DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment...
  53. pmc Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells
    Helene Bour-Jordan
    UCSF Diabetes Center, University of California at San Francisco, San Francisco, CA, USA
    Immunol Rev 229:41-66. 2009
    ..In this review, we discuss the connections between costimulation and Tregs that have changed the costimulation paradigm...
  54. doi The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance
    Taishin Akiyama
    Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokane dai, Minato ku, Tokyo 108 8639, Japan
    Immunity 29:423-37. 2008
    ..These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance...
  55. pmc Nonredundant roles for Stat5a/b in directly regulating Foxp3
    Zhengju Yao
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
    Blood 109:4368-75. 2007
    ..Therefore, we conclude that Stat5a/b have an essential, nonredundant role in regulating Treg cells, and that Stat3 and Stat5a/b appear to have opposing roles in the regulation of Foxp3...
  56. ncbi Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells
    Rafal Pacholczyk
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA
    Immunity 25:249-59. 2006
    ..Our results imply that higher TCR diversity on Foxp3(+) regulatory T cells helps these cells to match the specificities of autoreactive and naive T cells...
  57. ncbi Sonic hedgehog signalling in T-cell development and activation
    Tessa Crompton
    Immunobiology Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Nat Rev Immunol 7:726-35. 2007
    ..We also review the influence of hedgehog signalling in peripheral T-cell activation...
  58. doi The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator
    Yu Hikosaka
    Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770 8503, Japan
    Immunity 29:438-50. 2008
    ..These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance...
  59. pmc TGF-beta: a master of all T cell trades
    Ming O Li
    Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cell 134:392-404. 2008
    ..The unique mechanism of TGF-beta activation and the plasticity of TGF-beta signaling create a stage for TGF-beta to integrate signals from multiple cell types and environmental cues to regulate T cells...
  60. ncbi Continued maturation of thymic emigrants in the periphery
    Tamar E Boursalian
    Department of Immunology, University of Washington, Seattle, Washington 98195 7650, USA
    Nat Immunol 5:418-25. 2004
    ..In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery...
  61. ncbi Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation
    Ping Lan
    Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, USA
    Blood 108:487-92. 2006
    ..Thus, the humanized NOD/SCID mice described in this paper provide a powerful model system to study human immune function...
  62. ncbi Regulation of CD8+ T cell development by thymus-specific proteasomes
    Shigeo Murata
    Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo 113 8613, Japan
    Science 316:1349-53. 2007
    ..Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection...
  63. pmc Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery
    Tomoki Ito
    Department of Immunology and Center of Cancer Immunology Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Immunity 28:870-80. 2008
    ....
  64. ncbi Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells
    Daniel H D Gray
    Monash Immunology and Stem Cell Laboratories MISCL, Level 3, STRIP, Building 75, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia
    Blood 108:3777-85. 2006
    ..Overall, these studies show that the thymic stroma is a surprisingly dynamic population and may have a more direct role in negative selection than previously thought...
  65. pmc Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice
    Alfred Singer
    Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 8:788-801. 2008
    ..In this Review, we summarize recent advances in our understanding of the cellular and molecular events involved in lineage-fate decision and discuss them in the context of the major models of CD4/CD8-lineage choice...
  66. pmc Thymic development beyond beta-selection requires phosphatidylinositol 3-kinase activation by CXCR4
    Michelle L Janas
    Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Babraham, Cambridge, CB22 3AT England, UK
    J Exp Med 207:247-61. 2010
    ..These findings establish a role for CXCR4-mediated PI3K signaling that, together with signals from Notch and the preTCR, contributes to continued T cell development beyond beta-selection...
  67. pmc Intraclonal competition limits the fate determination of regulatory T cells in the thymus
    Jhoanne L Bautista
    Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Immunol 10:610-7. 2009
    ..Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection...
  68. pmc Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla
    Tom M McCaughtry
    Center for Immunology, Laboratory Medicine, and Pathology, University of Minnesota, Minneapolis, MN 55454, USA
    J Exp Med 205:2575-84. 2008
    ..Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion...
  69. doi The earliest thymic progenitors for T cells possess myeloid lineage potential
    J Jeremiah Bell
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nature 452:764-7. 2008
    ..Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered...
  70. ncbi A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127
    Christian A J Vosshenrich
    Unité des Cytokines et Développement Lymphoide, Institut National de la Santé et de la Recherche Médicale U668, Institut Pasteur, Paris F 75724, France
    Nat Immunol 7:1217-24. 2006
    ..We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets...
  71. ncbi Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function
    L Teixeira
    Division of Infectious Diseases and the Center for AIDS Research, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA
    AIDS 15:1749-56. 2001
    ..CONCLUSION: Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production...
  72. ncbi Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1
    Joseph T Opferman
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Department of Pathology and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:671-6. 2003
    ..Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes...
  73. pmc Stepwise development of MAIT cells in mouse and human
    Emmanuel Martin
    Laboratoire d Immunologie, Institut Curie, Paris, France
    PLoS Biol 7:e54. 2009
    ..Thus, their development follows a unique pattern at the crossroad of NKT and gammadelta T cells...
  74. pmc DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2
    Eleonora Candi
    Biochemistry Laboratory, Istituto Dermopatico dell Immacolata Istituto di Ricovero e Cura a Carattere Scientifico, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
    Proc Natl Acad Sci U S A 104:11999-2004. 2007
    ..The action of DeltaNp63 is not due to a direct regulation of TEC differentiation, but it is compatible with maintenance of their "stemness," the thymic abnormalities resulting from epithelial failure due to loss of stem cells...
  75. ncbi Two genetically separable steps in the differentiation of thymic epithelium
    M Nehls
    Deutsches Krebsforschungszentrum, Im Neuenheimer Feld, Heidelberg, Germany
    Science 272:886-9. 1996
    ..These results define the first genetically separable steps during thymic epithelial differentiation...
  76. ncbi Kruppel-like factor 2 regulates thymocyte and T-cell migration
    Corey M Carlson
    Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    Nature 442:299-302. 2006
    ..Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues...
  77. pmc Decision checkpoints in the thymus
    Andrea C Carpenter
    Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 11:666-73. 2010
    ..We focus on the divergence of alphabeta and gammadelta lineage cells and the elaboration of the alphabeta T cell repertoire, with special emphasis on the emergence of transcriptional programs that direct lineage decisions...
  78. ncbi Formation of a functional thymus initiated by a postnatal epithelial progenitor cell
    Conrad C Bleul
    Department of Developmental Immunology, Max Planck Institute of Immunobiology, Stuebeweg 51, D 79108 Freiburg, Germany
    Nature 441:992-6. 2006
    ..Thus, single epithelial progenitor cells can give rise to a complete and functional thymic microenvironment, suggesting that cell-based therapies could be developed for thymus disorders...
  79. ncbi Heterogeneity of thymic dendritic cells
    Li Wu
    The Walter and Eliza Hall Institute of Medical Research, 1G, Royal Parade, Parkville, VIC 3050, Australia
    Semin Immunol 17:304-12. 2005
    ..Thymic pDC can produce type-I interferon upon appropriate activation. However, their role in a steady state thymus is currently unclear...
  80. pmc Thymic emigration revisited
    Tom M McCaughtry
    Center for Immunology, Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455
    J Exp Med 204:2513-20. 2007
    ..Furthermore, emigration occurs via a strict "conveyor belt" mechanism, where the oldest thymocytes leave first...
  81. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
  82. ncbi An HMG-box-containing T-cell factor required for thymocyte differentiation
    S Verbeek
    Department of Immunology, University Hospital, Utrecht, The Netherlands
    Nature 374:70-4. 1995
    ..We conclude that Tcf-1 controls an essential step in thymocyte differentiation...
  83. pmc The thymus is a common target organ in infectious diseases
    Wilson Savino
    Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Inserm Fiocruz Associated Laboratory of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
    PLoS Pathog 2:e62. 2006
    ..In this context, thymus-centered immunotherapeutic approaches potentially represent a new tool for the treatment of severe infectious diseases...
  84. ncbi MicroRNAs modulate hematopoietic lineage differentiation
    Chang Zheng Chen
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 303:83-6. 2004
    ..Our results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development...
  85. doi Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms
    Thorsten B Feyerabend
    Institute for Immunology, University of Ulm, D 89081 Ulm, Germany
    Immunity 30:67-79. 2009
    ..Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus...
  86. pmc Quantitative impact of thymic selection on Foxp3+ and Foxp3- subsets of self-peptide/MHC class II-specific CD4+ T cells
    James J Moon
    Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Proc Natl Acad Sci U S A 108:14602-7. 2011
    ..Therefore, thymic selection of self-pMHCII-specific CD4(+) T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells...
  87. doi Autonomous versus dendritic cell-dependent contributions of medullary thymic epithelial cells to central tolerance
    Ludger Klein
    University of Munich, Institute for Immunology, Goethestr 31, 80336 Munich, Germany
    Trends Immunol 32:188-93. 2011
    ..We suggest that DC-dependent and autonomous tolerogenic functions of mTECs operate in parallel, and the underlying mechanisms remain to be established...
  88. ncbi The role of erk1 and erk2 in multiple stages of T cell development
    April M Fischer
    Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093 0377, USA
    Immunity 23:431-43. 2005
    ..Erk activity is essential for the process of positive selection, and it differentially affects CD4 and CD8 T cell maturation; yet, diminished expression itself is not sufficient to alter lineage commitment...
  89. ncbi Transcription factor GATA-3 is required for development of the T-cell lineage
    C N Ting
    The Departments of Medicine and Pathology, University of Chicago, Illinois 60637, USA
    Nature 384:474-8. 1996
    ..These findings suggest that GATA-3 is an essential and specific regulator of early thymocyte development...
  90. pmc Thymus-specific deletion of insulin induces autoimmune diabetes
    Yong Fan
    Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children s Hospital of Pittsburgh, Pittsburgh, PA 15201, USA
    EMBO J 28:2812-24. 2009
    ..Our observations may explain the rare cases of type 1 diabetes onset in very young children carrying diabetes-resistant HLA class II alleles. ID-TEC mice could serve as a new model for studying this pathology...
  91. pmc An essential role for nuclear factor kappaB in promoting double positive thymocyte apoptosis
    T Hettmann
    Departments of Medicine and Pathology, University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 189:145-58. 1999
    ..In addition, NF-kappaB is required for the alpha-CD3-mediated apoptosis of DP thymocytes through a pathway that involves the regulation of the antiapoptotic gene, bcl-xL...
  92. pmc Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors
    Song Baik
    MRC Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK
    Eur J Immunol 43:589-94. 2013
    ..Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts...
  93. pmc Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence
    Craig S Nowell
    MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
    PLoS Genet 7:e1002348. 2011
    ..Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development...
  94. ncbi Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium
    Simona W Rossi
    MRC Centre for Immune Regulation, Division of Immunity and Infection, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham B15 2TT, UK
    Nature 441:988-91. 2006
    ..Our findings resolve a long-standing issue in thymus development, and are important in relation to the development of cell-based strategies for thymus disorders and the possibility of restoring function of the atrophied adult thymus...
  95. ncbi Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration
    Maria L Allende
    Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 1821, USA
    J Biol Chem 279:15396-401. 2004
    ..The results indicated that the expression of the S1P(1) receptor on T-cells controls their exit from the thymus and entry into the blood and, thus, has a central role in regulating the numbers of peripheral T-cells...
  96. ncbi The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte development
    Soo Jung Yang
    Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Int Immunol 18:729-39. 2006
    ..We discuss possible mechanisms for positive selection by weak interactions in the presence of such preformed MHC II aggregate units in cTEC...
  97. ncbi Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty
    John M Murray
    School of Mathematics, University of NSW, Sydney, Australia
    Immunol Cell Biol 81:487-95. 2003
    ..7 year half-life of the productive thymus so that by age 55 only 5% of naive production arises from thymic export...
  98. pmc Spaceflight effects on T lymphocyte distribution, function and gene expression
    Daila S Gridley
    Department of Radiation Medicine, Loma Linda University, Loma Linda, CA 92354, USA
    J Appl Physiol (1985) 106:194-202. 2009
    ..Collectively, the data show that T cell distribution, function, and gene expression are significantly modified shortly after return from the spaceflight environment...
  99. ncbi Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin
    Yoko Hamazaki
    Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Nat Immunol 8:304-11. 2007
    ..Our results suggest that Aire(+) mTECs represent terminally differentiated cells in a unique lineage arising during thymic organogenesis...
  100. ncbi Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen
    H Pircher
    Department of Experimental Pathology, University Hospital, Zurich, Switzerland
    Nature 342:559-61. 1989
    ..Thus the same transgenic TCR-expressing T cells may be tolerized at different stages of their maturation and at different locations in the thymus depending on the antigen involved...
  101. pmc Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway
    Jonathan M Coquet
    Division of Immunology and 2 Division of Biological Stress Responses, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands
    J Exp Med 210:715-28. 2013
    ..Our data suggest that mTECs and DCs form dedicated niches in the thymic medulla, in which CD27-CD70 co-stimulation rescues developing Treg cells from apoptosis, subsequent to Foxp3 induction by TCR and CD28 signals...

Research Grants77

  1. Brain mast cells and Chronic Fatigue Syndrome
    Theoharis C Theoharides; Fiscal Year: 2013
    ..The proposed research is hypothesis-driven, is based on strong preliminary evidence, is innovative with high likelihood for novel findings with applicability to humans. ..
  2. Studying the effects of vitamin D on FOXP3 and IL-17 expression in human CD4+ T c
    Insoo Kang; Fiscal Year: 2010
    ..The results of the studies will advance our knowledge on how vitamin D can be used as a therapeutic agent to improve inflammation in humans. ..
  3. Novel SCID rat models for human cell transplantation studies
    Joseph C Ruiz; Fiscal Year: 2010
    ..There is a compelling need for an abundant and accessible supply of animals to screen for new therapeutic agents. Thus, if successful, this project would benefit many goals of public health. ..
  4. Knockdown of Gene Expression in Immune Cells in Humanized Mice
    Judy Lieberman; Fiscal Year: 2010
    ....
  5. Immune Development: Role of Milk Cell Transfer and Recipient Gender
    Ameae M Walker; Fiscal Year: 2013
    ..Results may also lead to the development of procedures for safely enhancing immunity in children. ..
  6. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2011
    ..This project is relevant to the NIH's mission because it will provide a resource to stimulate discovery, therapeutic application, and the development of new diagnostic tools. ..
  7. The molecular mechanism of Aire: partnering with DNA-PK
    Diane J Mathis; Fiscal Year: 2013
    ..Targeting certain of the new molecular interactions and pathways highlighted in this study may have therapeutic potential. ..
  8. 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. ..
  9. WI State Public Health Lab Capacity for SCID Screening
    CHARLES DENNIS BROKOPP; Fiscal Year: 2010
    ..Our SCID-NBS program will not only produce essential baseline data (i.e. incidence rates in the target population), it will detect SCID afflicted newborns born in year 01 through 03. ..
  10. Investigating the role of interleukin-22 in thymus function
    Jarrod Dudakov; Fiscal Year: 2013
    ....
  11. IL-22 in Thymic Regeneration
    Marcel R m van den Brink; Fiscal Year: 2013
    ....
  12. IL-22 in epithelial regeneration after allogeneic transplant
    Alan Hanash; Fiscal Year: 2013
    ..In addition, the career development goal of this project is to help Dr. Hanash transition into an independent investigator with his own laboratory and R01 funding. ..
  13. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2013
    ....
  14. Identification of stromal responses during castration-induced thymic regrowth.
    Howard T Petrie; Fiscal Year: 2013
    ..In addition to an in-depth understanding of the regrowth process, this project is expected to ultimately reveal potential new targets for thymic regeneration therapy. ..
  15. Development of transformed lactobacilli as a microbicide
    Richard B Markham; Fiscal Year: 2010
    ....
  16. Mechanisms of Peripheral Induction of T-Cell Tolerance
    MATTHEW FRANKLIN MESCHER; Fiscal Year: 2013
    ..The approach described in this application could lead to new methods for diagnosing diabetes and monitoring immunotherapy. ..
  17. Hunting for Endogenous Ligands for Invariant Natural Killer T Cells
    Peng George Wang; Fiscal Year: 2010
    ..This will also help researchers to develop methods to apply the principle into clinic application. ..
  18. Regulation of 22q11 Genes in Embroyonic and Adult Forebrain
    Anthony S LaMantia; Fiscal Year: 2013
    ..Thus, our studies help explain how a specific mutation can lead to changes in brain development and function that may underlie autism, mental retardation, ADHD, mood disorders and schizophrenia. ..
  19. DNA METHYLOME STUDY IN TYPE 1 DIABETES
    ART PETRONIS; Fiscal Year: 2009
    ..This effort may have a major impact on our understanding of autoimmune mechanisms in T1D and lead to new strategies in diagnostics and treatment of the disease. ..
  20. Regulation of Natural Killer T cell maturation, homeostasis and activation
    LOUISE M D'CRUZ; Fiscal Year: 2012
    ....
  21. The in vivo role of the mitochondrial p53 cell death program
    UTE MARTHA MOLL; Fiscal Year: 2013
    ..This is the thrust of this proposal. Furthermore, this proposal aims at gaining more mechanistic insight into how p53 works at the mitochondria to permeabilize these organelles. ..
  22. Regulation of Immunoglobulin Class Switch in Aged Mice
    Bonnie B Blomberg; Fiscal Year: 2013
    ..Studies of protein and mRNA stability, post translational regulation, and signal transduction pathways including MAPK, will determine key molecular elements in the control of Ig class switch in aged mice. ..
  23. Estrogen-T cell Interactions
    Prakash S Nagarkatti; Fiscal Year: 2013
    ..Thus, our studies are aimed at providing insights into the mechanism by which estrogens mediate their toxic effects on the immune system, thereby leading to the development of strategies for their prevention and treatment. ..
  24. Stem cell-mediated reversal of thymic involution in premature aging models
    Kenneth I Weinberg; Fiscal Year: 2010
    ....
  25. Identification of Stromal Responses During Castration Mediated Thymic Regrowth
    ANN VENABLES GRIFFITH; Fiscal Year: 2011
    ..In addition to an in-depth understanding of thymic stromal biology and the regrowth process, we expect to reveal potential targets for therapeutic approaches for thymic regeneration. ..
  26. Morphogenesis of mammalian gut endoderm
    Anna Katerina Hadjantonakis; Fiscal Year: 2012
    ..We will test the hypothesis that extraembryonic (visceral) endoderm is not an exclusively extraembryonic tissue using a genetic induced fate mapping approach. ..
  27. Basis for Lymphomagenesis in Akt2 Transgenic Mice
    Joseph R Testa; Fiscal Year: 2013
    ..abstract_text> ..
  28. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca H Buckley; Fiscal Year: 2010
    ..A O< -550 0.- 'c :.. (Op Ow. 'C7 .-" r-. w'- .-. .n_. -.z w01 (Da -v, E fl, .-, tin tin Q,0 ..
  29. MECHANISMS OF THE INDUCTION OF ORAL TOLERANCE
    Howard L Weiner; Fiscal Year: 2013
    ..We will investigate mechanisms to induce regulatory T cells by oral tolerance, which takes advantage of natural protective mechanisms that exist in the gut. ..
  30. Mechanisms used by skin dendritic cells to induce regulatory T cells
    Juliana Idoyaga; Fiscal Year: 2013
    ..Also, this knowledge is likely to be beneficial to the development new therapeutic targets to increase T reg, which in turn will lead to improved treatment of inflammatory skin diseases and their complications. ..
  31. Lipoproteins and Microbial Immunity
    HOBART WHITAKER HARRIS; Fiscal Year: 2013
    ....
  32. Role of HDAC7 in T-cell Development
    ERIC M VERDIN; Fiscal Year: 2010
    ..abstract_text> ..
  33. PROCESSED ANTIGEN CHARACTERIZATION BY MASS SPECTROMETRY
    Donald F Hunt; Fiscal Year: 2012
    ..abstract_text> ..
  34. CHARACTERIZATION OF NOVEL BUTADIENE-INDUCED PUTATIVE p53 TARGET GENES
    Perpetua M Muganda; Fiscal Year: 2010
    ..This knowledge will have an important vertical impact on butadiene risk assessment, as well as on the design of better means of therapeutic intervention after butadiene exposure. ..
  35. The Role of Stress in a Genetically Predisposed Epilepsy Model
    NIKKI TAMARA SAWYER; Fiscal Year: 2013
    ..Adrenal and thymus gland weights will allow us to determine if the R1648H mutants have chronically altered systemic levels of ..
  36. p38 MAP kinase in early thymocyte development
    Mercedes Rincon; Fiscal Year: 2013
    ..In addition, genetic mutations that may affect this pathway could determine a relatively higher susceptibility to develop T cell malignancies. ..
  37. TOX, a Novel Regulator of Thymocyte Selection
    JONATHAN G KAYE; Fiscal Year: 2013
    ....
  38. Interferon Effects on HIV Transmission in Human Models
    Judy Lieberman; Fiscal Year: 2013
    ....
  39. The role of Atg16L1 in Graft-Versus-Host-Disease
    VANESSA MARIE HUBBARD-LUCEY; Fiscal Year: 2013
    ..Finally, in order to study MNV infection in the GVHD setting we will perform allo-HSCT and infect mice WT and Atg16L1HM mice with MNV and follow the mice for survival and morbidity. ..
  40. Pathogenesis of HCV in a Novel Mouse Model
    Lishan Su; Fiscal Year: 2010
    ..These studies will establish the foundation for future study and shed light on novel therapeutic strategies for controlling HCV diseases. ..
  41. 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. ..
  42. Regulatory T cells in the influenza response of the aged
    Phyllis Jean Linton; Fiscal Year: 2009
    ....
  43. The GIT2-PIX-PAK complex in T cell migration, activation and arthritis
    Hyewon Phee; Fiscal Year: 2013
    ..These approaches will clarify the importance of the GIT2-PIX-PAK complex in normal T cell migration and activation and may provide insights into mechanisms relevant to T cell autoimmunity that could lead to novel therapeutics. ..
  44. CAML in T cell Development and Function
    Richard J Bram; Fiscal Year: 2011
    ....
  45. IMMUNOMODULATION OF TRANSPLANT REJECTION BY ANTI-CD3 MAB
    Jeffrey A Bluestone; Fiscal Year: 2013
    ....
  46. Antigen Identification in a Novel Model of Spontaneous Autoimmune Ovarian Disease
    Mickie H Cheng; Fiscal Year: 2012
    ..Finally, identifying the causative ovarian antigen may provide a potential therapeutic target for treatment and prevention of a significant cause of human ovarian failure and infertility. ..
  47. Nucleic Acid Enzymes and Nucleic Acids Studied at the Molecular Level
    Steven M Block; Fiscal Year: 2013
    ....
  48. REGULATION OF EBV INFECTION IN EPITHELIAL CELLS
    SHANNON CELESTE KENNEY; Fiscal Year: 2013
    ..The results of these studies may lead to new treatments for AIDS-related lymphomas and oral hairy leukoplakia. ..
  49. Therapeutic Immunoregulation Mediated by TGF-beta-induced iTregs in Autoimmune Ar
    Song Guo Zheng; Fiscal Year: 2013
    ..If successful, this project will also have a direct clinical relevance and possibly provide a novel approach to treat RA and other autoimmune diseases which may not have the severe side effect(s) characteristic of current therapies. ..
  50. Hematological consequences of FLVCR, a cytoplasmic heme export protein
    Janis L Abkowitz; Fiscal Year: 2013
    ..We can thus determine whether these different lineages share regulatory pathways. Together these studies should provide significant insights into heme signaling and toxicities during hematopoietic cell differentiation. ..
  51. Role of the thymic epithelium on the outcome of allogeneic transplantation
    Konstantina Alexandropoulos; Fiscal Year: 2013
    ....
  52. Optimizing Human B and T Cell Vaccines Against HIV Using Humanized BLT Mice
    Todd M Allen; Fiscal Year: 2013
    ..This model will also enable us to rapidly test iterative vaccine design approaches to further optimize cellular immune responses to HIV. ..
  53. Immunoregulation of Schistosomiasis
    Miguel J Stadecker; Fiscal Year: 2013
    ..Their ultimate objective is the design of focused, realistic and practical strategies for amelioration of disease, which could be amenable for consideration and implementation in the human patient population. ..
  54. Therapeutic Antibodies for CMV
    WILLIAM ROBERT USINGER; Fiscal Year: 2013
    ..The final deliverable from this project will be an IND-ready native human therapeutic antibody to HCMV, which is highly effective at preventing infection of all relevant cell types by a broad range of HCMV strains. ..
  55. 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. ..
  56. Steroid Receptors and Transcriptional Control of Thymic Rebound
    Nancy R Manley; Fiscal Year: 2011
    ..The current proposal seeks to identify the cellular and molecular targets of androgen signaling in the postnatal thymus and during thymic rebound. ..
  57. The Role of Heparan Sulfate in the B cell response
    DAMIAN LUIS TRUJILLO; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: The work we prose here may help in understanding of the antibody response against infectious disease. Furthermore, understanding of the topic may enhance vaccine development. ..
  58. TGF-beta and Common gamma-Chain Cytokine Crosstalk in T Cell Regulation
    Ming Li; Fiscal Year: 2013
    ..Successful completion of the projects outlined in this proposal will generate mechanistic insights into the crosstalk between TGF-beta and the common gamma-chain cytokines in T cell regulation. ..
  59. Pig to human thymic xenotransplantation
    Megan Sykes; Fiscal Year: 2013
    ....
  60. Molecular basis for age-related thymic involution and rejuvenation
    Dong Ming Su; Fiscal Year: 2013
    ..These studies will lay the groundwork for restoring thymic dysfunction and extending the functional lifespan of human cellular immunity. ..
  61. 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. ..
  62. THE V(D)J RECOMBINATION REACTION AND ITS IMPACT ON LYMPHOCYTE DEVELOPMENT
    Barry P Sleckman; Fiscal Year: 2013
    ....
  63. 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. ..
  64. Positron Emission Tomography to Evaluate Thymic Function
    Laura Napolitano; Fiscal Year: 2006
    ..abstract_text> ..
  65. HIV and Plasmacytoid dendritic cells in the thymus
    Christel Uittenbogaart; Fiscal Year: 2007
    ..Information gained from the proposed experiments will have implications for the treatment of HIV infected patients with immunomodulatory therapies, such as IFN-alpha. ..
  66. Hemophilia A: Intrathymic Delivery for Tolerance and Longterm Expression of FVIII
    William Raschke; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  67. HIV and Plasmacytoid dendritic cells in the thymus
    Christel Uittenbogaart; Fiscal Year: 2002
    ..The study of pDC in HIV infection of the thymus provides an opportunity to improve our understanding of HIV induced immunodeficiency. ..
  68. THYMIC LYMPHOCYTE DEVELOPMENT
    Irving Weissman; Fiscal Year: 2004
    ..abstract_text> ..
  69. AUTOREACTIVITY TO AChR IN THE THYMUS OF MG PATIENTS
    Sonia Berrih Aknin; Fiscal Year: 2004
    ....
  70. Evaluation of thymus function in lentivirus disease
    Lawrence Mathes; Fiscal Year: 2009
    ..abstract_text> ..
  71. THYMIC FUNCTION IN ADULTS WITH HIV1 DISEASE
    Joseph McCune; Fiscal Year: 2002
    ..McCune's lab and a mass spectrometer maintained in Dr. Hellerstein's lab. ..
  72. IMMUNOBIOLOGY OF AUTOIMMUNITY
    Vanda Lennon; Fiscal Year: 1990
    ....
  73. Sex steroids and the thymus
    GILBERT KERSH; Fiscal Year: 2006
    ..abstract_text> ..
  74. SCREEN FOR LYMPHOID MUTANTS
    Nikolaus Trede; Fiscal Year: 2004
    ..abstract_text> ..
  75. THYMIC TRANSPLANTATION IN COMPLETE DIGEORGE SYNDROME
    MARY MARKERT; Fiscal Year: 2009
    ..abstract_text> ..
  76. RECONSTRUCTION OF THE THYMUS AFTER HIV INFECTION BY IL-7
    Kenneth Weinberg; Fiscal Year: 1999
    ..The goal of these studies is to develop an IL-7 gene therapy trial in the next 2 years. ..
  77. Genetic analysis of thymus organogenesis
    Nancy Manley; Fiscal Year: 2007
    ..abstract_text> ..