interleukin 2 receptors

Summary

Summary: Receptors present on activated T- and B-cells as a complex consisting of a 55-kDa peptide, which reacts with the anti-Tac monoclonal antibody, and a 75-kDa non-Tac interleukin-2-binding peptide. The receptor is present in two forms, one with a very high affinity and the other with low affinity for IL-2. The high-affinity form appears to mediate exclusively the growth-promoting response to IL-2. The receptor is present in large numbers on resting HUMAN T-LYMPHOTROPIC VIRUS 1 leukemia cells, but not on normal resting cells.

Top Publications

  1. ncbi Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
    Jason D Fontenot
    Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195, USA
    Nat Immunol 4:330-6. 2003
  2. pmc Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3
    Wanjun Chen
    Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 198:1875-86. 2003
  3. 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
  4. 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
  5. pmc Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood
    H Jonuleit
    Department of Dermatology, University of Mainz, D 55101 Mainz, Germany
    J Exp Med 193:1285-94. 2001
  6. ncbi CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, Leishmania major infection, and colitis in mice
    Damo Xu
    Department of Immunology and Bacteriology, University of Glasgow, Glasgow, Scotland, United Kingdom
    J Immunol 170:394-9. 2003
  7. 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
  8. ncbi Regulatory T cells in transplantation tolerance
    Kathryn J Wood
    Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
    Nat Rev Immunol 3:199-210. 2003
  9. pmc Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta
    K Nakamura
    Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 194:629-44. 2001
  10. ncbi Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer
    E Y Woo
    Department of Surgery, Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 61:4766-72. 2001

Detail Information

Publications348 found, 100 shown here

  1. ncbi Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
    Jason D Fontenot
    Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195, USA
    Nat Immunol 4:330-6. 2003
    ..Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25- T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function...
  2. pmc Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3
    Wanjun Chen
    Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 198:1875-86. 2003
    ..Finally, in a murine asthma model, coadministration of these TGF-beta-induced suppressor T cells prevented house dust mite-induced allergic pathogenesis in lungs...
  3. 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...
  4. 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...
  5. pmc Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood
    H Jonuleit
    Department of Dermatology, University of Mainz, D 55101 Mainz, Germany
    J Exp Med 193:1285-94. 2001
    ..However, the refractory state of CD4(+)CD25(+) T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties...
  6. ncbi CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, Leishmania major infection, and colitis in mice
    Damo Xu
    Department of Immunology and Bacteriology, University of Glasgow, Glasgow, Scotland, United Kingdom
    J Immunol 170:394-9. 2003
    ..Our results therefore document that CD4+CD25+ regulatory T cells suppress both Th1 and Th2 cells and that these regulatory T cells have a profound therapeutic potential against diseases induced by both Th1 and Th2 cells in vivo...
  7. 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...
  8. ncbi Regulatory T cells in transplantation tolerance
    Kathryn J Wood
    Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
    Nat Rev Immunol 3:199-210. 2003
    ....
  9. pmc Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta
    K Nakamura
    Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 194:629-44. 2001
    ..This, plus the fact that we could find no evidence that a soluble factor mediates suppression, strongly suggests that CD4(+)CD25(+) T cells exert immunosuppression by a cell-cell interaction involving cell surface TGF-beta1...
  10. ncbi Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer
    E Y Woo
    Department of Surgery, Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 61:4766-72. 2001
    ..These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients...
  11. pmc Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells
    Sayuri Yamazaki
    Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA
    J Exp Med 198:235-47. 2003
    ..The capacity to expand CD25+ CD4+ T cells provides DCs with an additional mechanism to regulate autoimmunity and other immune responses...
  12. ncbi CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
    Yasmine Belkaid
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 420:502-7. 2002
    ....
  13. 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
    ....
  14. ncbi Interleukin-2 is essential for CD4+CD25+ regulatory T cell function
    Maurus de la Rosa
    Deutsches Rheuma ForschungsZentrum Berlin, Berlin, Germany
    Eur J Immunol 34:2480-8. 2004
    ..We propose the parakrine uptake of soluble mediators as a flexible mechanism to adapt Treg activity to the strength of the responder T cell reaction...
  15. ncbi Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
    Tyler J Curiel
    Tulane University Health Science Center, New Orleans, Louisiana 70112, USA
    Nat Med 10:942-9. 2004
    ..This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer...
  16. ncbi Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance
    Jun Shimizu
    Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
    Nat Immunol 3:135-42. 2002
    ..Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease...
  17. pmc Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation
    Petra Hoffmann
    Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CA 94305, USA
    J Exp Med 196:389-99. 2002
    ..Our results demonstrate that the balance of donor-type CD4(+)CD25(+) T(reg) and conventional CD4(+)CD25(-) T cells can determine the outcome of aGVHD...
  18. 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...
  19. pmc Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide
    Iris Caramalho
    Instituto Gulbenkian de Ciencia, 2781 901 Oeiras, Portugal
    J Exp Med 197:403-11. 2003
    ..These findings provide the first evidence that Treg respond directly to proinflammatory bacterial products, a mechanism that likely contributes to the control of inflammatory responses...
  20. ncbi An essential role for Scurfin in CD4+CD25+ T regulatory cells
    Roli Khattri
    Celltech R and D Inc, 1631 220th Street SE, Bothell, Washington 98021, USA
    Nat Immunol 4:337-42. 2003
    ..The forced expression of Foxp3 also delays disease in CTLA-4-/- mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the T(R) cell lineage...
  21. ncbi Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment
    D M Willerford
    Howard Hughes Medical Institute, Department of Pediatrics, Children s Hospital, Boston, Massachusetts 02115, USA
    Immunity 3:521-30. 1995
    ..Thus, IL-2R alpha is essential for regulation of both the size and content of the peripheral lymphoid compartment, probably by influencing the balance between clonal expansion and cell death following lymphocyte activation...
  22. ncbi GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations
    Simona Ronchetti
    Eur J Immunol 34:613-22. 2004
    ..These results indicate a novel function for GITR as costimulatory molecule of T cell subsets...
  23. 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...
  24. pmc Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens
    Einar M Aandahl
    Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California 94110, USA
    J Virol 78:2454-9. 2004
    ..We propose that chronic viral infections lead to induction of suppressive T(R) cells that inhibit the antiviral immune response...
  25. pmc Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4
    T Takahashi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 192:303-10. 2000
    ..This unique function of CTLA-4 could be exploited to potentiate T cell-mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity...
  26. pmc Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells
    Jochen Huehn
    Experimentelle Rheumatologie, Medizinische Klinik, Charite, Humboldt Universitaet, Schumannstr 21 22, 10117 Berlin, Germany
    J Exp Med 199:303-13. 2004
    ..Accordingly, alphaE -expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis...
  27. ncbi The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality
    Patricia A Taylor
    University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis 55455, USA
    Blood 99:3493-9. 2002
    ..CD4(+)CD25(+) cells warrant consideration as an exciting new modality of cellular therapy for the inhibition of undesirable autologous and allogeneic responses...
  28. ncbi Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells
    W F Ng
    Department of Immunology, Hammersmith Campus, Imperial College School of Medicine, London, United Kingdom
    Blood 98:2736-44. 2001
    ..Comparison with rodent CD4(+)CD25(+) cells suggests that this population may play a key role in the prevention of autoimmune diseases in humans...
  29. ncbi Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor
    K H Grabstein
    Immunex Research and Development Corporation, Seattle, WA 98101
    Science 264:965-8. 1994
    ..Monoclonal antibodies to the beta chain of the IL-2 receptor inhibited the biological activity of IL-15, and IL-15 competed for binding with IL-2, indicating that IL-15 uses components of the IL-2 receptor...
  30. ncbi Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma
    Udaya K Liyanage
    Alvin J Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 169:2756-61. 2002
    ..These T(reg) may mitigate the immune response against cancer, and may partly explain the poor immune response against tumor Ags...
  31. pmc CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses
    Susmit Suvas
    Department of Microbiology, University of Tennessee, Knoxville, TN 37996 0845, USA
    J Exp Med 198:889-901. 2003
    ..Thus, controlling suppressor effects at the time of vaccination could result in more effective immunity...
  32. ncbi IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells
    Sigrid Dubois
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 17:537-47. 2002
    ..Finally, these complexes on activated monocytes present IL-15 in trans to target cells such as CD8(+) T cells that express only IL-2/15Rbeta and gammac upon cell-cell interaction...
  33. ncbi Neuropilin-1: a surface marker of regulatory T cells
    Dunja Bruder
    Eur J Immunol 34:623-30. 2004
    ..Thus, Nrp1 constitutes a useful surface marker to distinguish Treg cells from both naive and recently activated CD4+CD25+ non-regulatory T cells...
  34. ncbi Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta
    H Suzuki
    Amgen Institute, Toronto, Ontario, Canada
    Science 268:1472-6. 1995
    ..Thus, IL-2R beta is required to keep the activation programs of T cells under control, to maintain homeostasis, and to prevent autoimmunity...
  35. 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...
  36. ncbi CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion
    Maria A Curotto de Lafaille
    Molecular Pathogenesis Program, Skirball Institute, and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Immunol 173:7259-68. 2004
    ..The maintenance of CD25 expression by CD4(+)CD25(+) cells depends on IL-2 secreted by cotransferred CD4(+)CD25(-) or by Ag-stimulated T cells in peripheral lymphoid organs...
  37. ncbi CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells
    Pau Serra
    Julia McFarlane Diabetes Research Centre, University of Calgary, Faculty of Medicine, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
    Immunity 19:877-89. 2003
    ..Thus, in at least some genetic backgrounds, CD154-CD40 interactions and innate stimuli release immature DCs from suppression by CD4+CD25+ T cells...
  38. ncbi CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions
    Susmit Suvas
    Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA
    J Immunol 172:4123-32. 2004
    ..Our results decipher the in vivo role of T(reg) in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease...
  39. ncbi Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers
    Afonso R M Almeida
    Lymphocyte Population Biology, Unité de Recherche Associée Centre National de la Recherche Scientifique 1961, Institut Pasteur, Paris, France
    J Immunol 169:4850-60. 2002
    ....
  40. 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...
  41. ncbi Modulation of tryptophan catabolism by regulatory T cells
    Francesca Fallarino
    Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
    Nat Immunol 4:1206-12. 2003
    ..Thus, regulation of immunosuppressive tryptophan catabolism in dendritic cells might represent a major mechanism of action of T(R) cells...
  42. ncbi TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice
    Kazuhiko Nakamura
    Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N238, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 172:834-42. 2004
    ..Together, these studies demonstrate that TGF-beta1 produced by CD4+CD25+ T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation...
  43. ncbi Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells
    Christian Mottet
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    J Immunol 170:3939-43. 2003
    ..These studies suggest that manipulation of CD4(+)CD25(+) T cells may be beneficial in the treatment of chronic inflammatory diseases...
  44. pmc Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells
    Mindi R Walker
    Diabetes Program, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, Washington 98101, USA
    J Clin Invest 112:1437-43. 2003
    ..These data also raise the possibility that a failure to generate peripheral TR cells properly may contribute to autoimmune disease and suggest a possible therapeutic role for FoxP3 in the treatment of such diseases...
  45. 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...
  46. ncbi CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25- subpopulations
    L A Stephens
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    J Immunol 165:3105-10. 2000
    ..Phenotypic analysis of human thymocytes showed the presence of CD25+ cells in the same proportions as in rat thymus. The possible developmental relationship between CD25+ and CD25- regulatory T cells is discussed...
  47. ncbi CD4+CD25high regulatory cells in human peripheral blood
    C Baecher-Allan
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115
    J Immunol 167:1245-53. 2001
    ....
  48. ncbi CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor
    Rebecca S McHugh
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 16:311-23. 2002
    ..Importantly, antibodies to GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset...
  49. pmc Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells
    Megan K Levings
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Via Olgettina 58, Milan 20132, Italy
    J Exp Med 196:1335-46. 2002
    ..Together these data indicate that naturally occurring human CD25(+)CD4(+) T cells are distinct from IL-10-producing Tr1 cells...
  50. ncbi B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes
    B Salomon
    Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 12:431-40. 2000
    ..The results suggest that the CD28/ B7 costimulatory pathway is essential for the development and homeostasis of regulatory T cells that control spontaneous autoimmune diseases...
  51. ncbi Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis
    Amanda L Cox
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
    Eur J Immunol 35:3332-42. 2005
    ..We speculate that CCL21 and IL-15 responses to lymphopaenia may be suboptimal in multiple sclerosis...
  52. ncbi B cells and professional APCs recruit regulatory T cells via CCL4
    R S Bystry
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Nat Immunol 2:1126-32. 2001
    ..This suggested that the recruitment of regulatory T cells to B cells and APCs by CCL4 plays a central role in the normal initiation of T cell and humoral responses, and failure to do this leads to autoimmune activation...
  53. ncbi CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis
    Mary E Morgan
    Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 48:1452-60. 2003
    ..We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen-induced arthritis (CIA)...
  54. ncbi Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression
    S Dubois
    Groupe de Recherche Cytokines et Récepteurs, Unité INSERM 463, Institut de Biologie, 9 quai Moncousu, 44035 Nantes Cedex 01, France
    J Biol Chem 274:26978-84. 1999
    ..Together, our data indicate that exon 2 splicing of human IL-15Ralpha is a natural process that might play regulatory roles at different levels...
  55. ncbi Development and activation of regulatory T cells in the human fetus
    Tom Cupedo
    Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
    Eur J Immunol 35:383-90. 2005
    ..Upon activation, FoxP3+CD4+CD25+ Treg suppress potentially deleterious responses by autoreactive lymphocytes and maintain homeostasis within the developing fetus...
  56. pmc Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells
    Helene C Dujardin
    Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France
    Proc Natl Acad Sci U S A 101:14473-8. 2004
    ..This study demonstrates that the peripheral immune system of newborn mice is endowed of a remarkable regulatory potential, which develops considerably in the absence of thymic supply...
  57. ncbi Control of immune homeostasis by naturally arising regulatory CD4+ T cells
    Marc Gavin
    Department of Immunology, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195, USA
    Curr Opin Immunol 15:690-6. 2003
    ..T(R) cells are capable of robust antigen-driven proliferation in vivo, and may participate in clonal expansion in response to infection, similar to all other adaptive immune lineages...
  58. pmc Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor
    J G Giri
    Immunex Research and Development Corporation, Seattle, WA 98101, USA
    EMBO J 14:3654-63. 1995
    ..IL-15R alpha is structurally similar to IL-2R alpha; together they define a new cytokine receptor family. The distribution of IL-15 and IL-15R alpha mRNA suggests that IL-15 may have biological activities distinct from IL-2...
  59. ncbi Activated T lymphocytes in Type 2 diabetes: implications from in vitro studies
    Frankie B Stentz
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Curr Drug Targets 4:493-503. 2003
    ..Due to the accessibility of obtaining these cells from patients, activated T-lymphocytes offer the potential of studying diabetes and other disease in human subjects...
  60. ncbi Antigen-specific regulatory T cells--their induction and role in infection
    Kingston H G Mills
    Immune Regulation Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland
    Semin Immunol 16:107-17. 2004
    ..Tr1 or Th3 cells are capable of suppressing Th1 and Th2 responses and function in infection to limit pathogen-induced immunopathology, but can also be exploited in therapies for immune-mediated diseases...
  61. ncbi Loss of tolerance and autoimmunity affecting multiple organs in STAT5A/5B-deficient mice
    Jonathan W Snow
    Gladstone Institute of Virology and Immunology, and Department of Microbiology and Immunology, University of California, San Francisco, CA 94114, USA
    J Immunol 171:5042-50. 2003
    ..These data provide strong evidence for a requirement for STAT5 in the maintenance of tolerance in vivo...
  62. ncbi The Sushi domain of soluble IL-15 receptor alpha is essential for binding IL-15 and inhibiting inflammatory and allogenic responses in vitro and in vivo
    M Orchardson
    Department of Immunology and Bacteriology and Center of Rheumatic Disease, University of Glasgow, Glasgow, United Kingdom
    J Immunol 167:277-82. 2001
    ..Thus, the Sushi domain is critical for the functional activity of sIL-15Ralpha...
  63. ncbi Control of intestinal inflammation by regulatory T cells
    B Singh
    Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
    Immunol Rev 182:190-200. 2001
    ....
  64. ncbi Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation
    Edward Y Woo
    Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    J Immunol 168:4272-6. 2002
    ..Together these results suggest that the CD4(+)CD25(+) T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer...
  65. ncbi MHC class II expression identifies functionally distinct human regulatory T cells
    Clare Baecher-Allan
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 176:4622-31. 2006
    ..Thus, the direct ex vivo expression of MHC-II in the context of CD25(high) identifies a mature, functionally distinct regulatory T cell population involved in contact-dependent in vitro suppression...
  66. ncbi CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism
    Takatoku Oida
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 170:2516-22. 2003
    ..The regulatory function of CD25(-)LAP(+) cells was abrogated in vivo by anti-TGF-beta mAb. These results identify a new TGF-beta-dependent regulatory CD4(+) T cell phenotype that is CD25(-) and LAP(+)...
  67. pmc Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells
    Masahide Tone
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom
    Proc Natl Acad Sci U S A 100:15059-64. 2003
    ..Expression was controlled by the transcription factor NF-1 and potentially by alternative splicing of mRNA destabilization sequences...
  68. pmc Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice
    J J Peschon
    Immunex Research and Development Corporation, Seattle, Washington 98101
    J Exp Med 180:1955-60. 1994
    ..Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7...
  69. pmc Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function
    M K Levings
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET, Via Olgettina 58, Milan, Italy 20132
    J Exp Med 193:1295-302. 2001
    ....
  70. ncbi Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product
    S Ruben
    Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, NJ 07110
    Science 241:89-92. 1988
    ..A model is presented whereby regulation of cellular gene expression by the HTLV-I tax gene product occurs via an indirect mechanism that may involve a post-translational modification of preexistent cellular transcription factors...
  71. ncbi Modulation of Fas-dependent apoptosis: a dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells
    Alice Banz
    Institut National de la Sante et de la Recherche Medicale, Unité 345, Institut Necker, Paris, France
    J Immunol 169:750-7. 2002
    ....
  72. ncbi The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2 response elements
    H P Kim
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 15:159-72. 2001
    ..Thus, the IL-2 inducibility of the IL-2Ralpha gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites...
  73. ncbi Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance
    Luis Graca
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    J Immunol 168:5558-65. 2002
    ..Further characterization of the differentially expressed genes may lead to the development of diagnostic tests to monitor the tolerant state...
  74. ncbi CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4
    Hiroshi Kataoka
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba 260 8670, Japan
    Int Immunol 17:421-7. 2005
    ..Furthermore, CD25(+)CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression...
  75. ncbi Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance
    S Gregori
    Roche Milano Ricerche, Milan, Italy
    J Immunol 167:1945-53. 2001
    ....
  76. ncbi Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients
    Laurence Weiss
    Institut National de la Santé et de la Recherche Médicale U430, University of Paris V, France
    Blood 104:3249-56. 2004
    ..Taken together, our results suggest that persistence of HIV antigens might trigger the expansion of CD4(+)CD25(+) regulatory T cells, which might induce a tolerance to HIV in vivo...
  77. pmc Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells
    Mary Jo Turk
    The Swim Across America Laboratory of Tumor Immunology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Exp Med 200:771-82. 2004
    ..These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor...
  78. ncbi Natural regulatory T cells in infectious disease
    Yasmine Belkaid
    Division of Molecular Immunology, Cincinnati Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
    Nat Immunol 6:353-60. 2005
    ..We describe here various situations in which the balance between natural T(reg) cells and effector immune functions influences the outcome of infection and discuss how manipulating this equilibrium might be exploited therapeutically...
  79. ncbi Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration
    X Zhang
    Center for Neurologic Diseases, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 167:4245-53. 2001
    ..These results demonstrate an Ag-specific in vivo method to activate CD25(+)CD4(+) regulatory T cells and suggest that they may be involved in oral tolerance...
  80. pmc Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells
    A Iellem
    Roche Milano Ricerche, Milano I-20132, Italy
    J Exp Med 194:847-53. 2001
    ..Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation...
  81. ncbi Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population
    L S Taams
    Department of Clinical Immunology, Royal Free and University College Medical School, London, GB
    Eur J Immunol 31:1122-31. 2001
    ..Further studies into their role in normal and pathological situations in humans are clearly essential...
  82. ncbi CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation
    Matthias Edinger
    Division of Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA
    Nat Med 9:1144-50. 2003
    ..Thus, CD4+CD25+ T cells are potent regulatory cells that can separate GVHD from GVT activity mediated by conventional donor T cells...
  83. pmc CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms
    Kevin J Maloy
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, United Kingdom
    J Exp Med 197:111-9. 2003
    ..Thus, CD4(+)CD25(+) T(R) cells do not only suppress adaptive T cell responses, but are also able to control pathology mediated by innate immune mechanisms...
  84. ncbi Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling
    Louise M D'Cruz
    Research Institute of Molecular Pathology, 1030 Vienna, Austria
    Nat Immunol 6:1152-9. 2005
    ....
  85. ncbi Association between immunity and prognostic factors in early stage breast cancer patients before adjuvant treatment
    M E Sabbioni
    Medical Division Lory Haus, University Hospital Inselspital, Berne, Switzerland
    Breast Cancer Res Treat 59:279-87. 2000
    ..The association of known prognostic factors with immune cell counts and beta2-microglobulin and soluble IL-2 receptor (sIL-2r) serum levels as markers of activation of the immune system was investigated in breast cancer...
  86. ncbi Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo
    Susanna Grundström
    Active Biotech Research AB, Lund, Sweden
    J Immunol 170:5008-17. 2003
    ....
  87. pmc T cell regulation as a side effect of homeostasis and competition
    Thomas Barthlott
    Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Exp Med 197:451-60. 2003
    ....
  88. pmc Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15
    J G Giri
    Immunex Research and Development Corporation, Seattle, WA 98101
    EMBO J 13:2822-30. 1994
    ..The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component...
  89. ncbi Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's
    M Hatakeyama
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Science 244:551-6. 1989
    ..Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA...
  90. pmc Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis
    Estelle Bettelli
    Center for Neurologic Diseases, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Exp Med 200:79-87. 2004
    ..Although the two transcription factors, STAT1 and T-bet, both induce IFN-gamma gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses...
  91. ncbi CD28 disruption exacerbates inflammation in Tgf-beta1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-beta1
    Mizuko Mamura
    Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bldg 41, 41 Library Drive MSC 5055, Bethesda, MD 20892 5055, USA
    Blood 103:4594-601. 2004
    ....
  92. 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...
  93. pmc Age-dependent levels of select immunological mediators in sera of healthy children
    U Sack
    Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany
    Clin Diagn Lab Immunol 5:28-32. 1998
    ..Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution...
  94. ncbi IL-15/IL-15Ralpha intracellular trafficking in human melanoma cells and signal transduction through the IL-15Ralpha
    R Pereno
    U506 INSERM Hôpital Paul Brousse 94807 Villejuif, France
    Oncogene 19:5153-62. 2000
    ..Thus, IL-15Ralpha controls NF-kappaB activation, however differences in the intracellular trafficking of the IL-15 and/or IL-15Ralpha suggest a different biological role for this complex in MELP versus MELREO cells...
  95. ncbi Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells
    E Suri-Payer
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, SM722, Boston, MA 02115, USA
    J Autoimmun 16:115-23. 2001
    ....
  96. ncbi Differential T cell costimulatory requirements in CD28-deficient mice
    A Shahinian
    Department of Medical Biophysics and Immunology, University of Toronto, Canada
    Science 261:609-12. 1993
    ..Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist...
  97. ncbi Regulatory T cells in the control of immune pathology
    K J Maloy
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Nat Immunol 2:816-22. 2001
    ..We will review here recent findings in these areas, outline a model for how T(R) cells may inhibit the development of immune pathology and discuss potential therapeutic benefits that may arise from the manipulation of T(R) cell function...
  98. ncbi Human T regulatory cells can use the perforin pathway to cause autologous target cell death
    William J Grossman
    Department of Pediatrics, Division of Hematology Oncology, St Louis Children s Hospital, St Louis, MO 63110, USA
    Immunity 21:589-601. 2004
    ..This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses...
  99. ncbi Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease
    Britt E Anderson
    Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar St, PO Box 208035, New Haven, CT 06520 8035, USA
    Blood 104:1565-73. 2004
    ..Additional CD4+CD25+ cells also promoted healing of established lesions, suggesting that their effects persist during the evolution of cGVHD...
  100. ncbi CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice
    Shohei Hori
    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Eur J Immunol 32:1282-91. 2002
    ..Our results indicate an essential role for CD25(+)CD4(+) T cells in the control of PC-driven immunopathology, and suggest that in immunocompromised hosts PC pneumonia may result from a deficiency in regulatory T cells...
  101. ncbi Circulating CD4+CD25+ T regulatory cells are not altered in multiple sclerosis and unaffected by disease-modulating drugs
    Prabhakar Putheti
    Division of Neuroimmunology, Neurotec Department, Karolinska Institute, Stockholm, Sweden
    J Clin Immunol 24:155-61. 2004
    ..This study suggests that levels of circulating CD4(+)CD25(+) Tr cells and CD4(+)CD25(high) Tr cells are not altered in MS, and are unaffected by substances currently used to modulate the disease...

Research Grants63

  1. Monoclonal Antibodies Against T-Regulatory Cells
    Alan Epstein; Fiscal Year: 2005
    ..Along with LEC/NHS76, this new antibody/drug conjugate should be applicable to use in humans and may provide clinicians with a vital weapon in our relentless effort to treat cancer. ..
  2. Nebraska/Kansas Blood and Marrow Transplant Research Network
    JULIE MARIE VOSE; Fiscal Year: 2013
    ..The BMT/CTN including our consortium will be the only clinical cooperative group to accomplish this goal. ..
  3. T1D:Investigating the Gut Microbiome, Urinary Proteome and Metabolome
    Ramana Madupu; Fiscal Year: 2011
    ..We propose to study the complex interplay of environmental, immunological and genetic factors to discover molecular signatures with a potential to advance clinical diagnosis and therapy at or before the onset of T1D. ..
  4. Chronic alcohol abuse disrupts CD8+T cell function
    Annette J Schlueter; Fiscal Year: 2013
    ..Vertebrate Animals 193-195 8. Literature Cited , 195-199 9. Consortium/Contractual Arrangements '. N/A 10. Consultants/Collaborators N/A Appendices on CD: 5 Publications PHS 398 (Rev. 04/06) Page 168 Form Page 3 ..
  5. Bridging Pediatric and Adult Biomarkers of Graft-Versus-Host-Disease
    Jamie L Renbarger; Fiscal Year: 2013
    ..Ultimately, we propose the discovery of a GVHD-specific drug to increase efficacy and lower toxicity. ..
  6. NK cells in CNS inflammation and autoimmunity
    Fu Dong Shi; Fiscal Year: 2013
    ..abstract_text> ..
  7. CD4+ Memory T-Cells in Human Tumor Microenvironment
    Richard B Bankert; Fiscal Year: 2013
    ..We intend to determine what is responsible for the apparent functional arrest of the tumor-specific T cells and to design and test ways to prevent and/or reverse the shutdown of these cells once they reach the tumor. ..
  8. Role of MEK1 in T cell function in asthma
    Rafeul Alam; Fiscal Year: 2013
    ..The proposal is important because it addresses the mechanism of persistence of airway inflammation in asthma. The results of this study will lead to the development of novel therapeutic modalities for asthma. ..
  9. MOLECULAR ENGINEERING OF IL-2 FOR THE TREATMENT AND PREVENTION OF TYPE I DIABETES
    AARON MICHAEL RING; Fiscal Year: 2013
    ..Thus, through these multidisciplinary and translational studies, we will advance new candidate T1D therapies for clinical development. ! ..
  10. Development of Intestinal Immune Regulation in Human Infants
    JOERN HENDRIK WEITKAMP; Fiscal Year: 2013
    ..This proposal develops novel translational approaches to identify cellular and molecular targets for reducing the pathologic host immune response in NEC and to detect infants at highest risk of this devastating disease. ..
  11. Linking Genetic Variation in the PTPN2 Gene to Autoimmune Disease Susceptibility
    Jane Hoyt Buckner; Fiscal Year: 2010
    ..This gene is associated with multiple autoimmune diseases;so understanding the impact of this gene on the human immune system will help us understand the pathways which lead to autoimmunity. ..
  12. Homing and Homeostasis of Regulatory T cells
    Daniel J Campbell; Fiscal Year: 2012
    ..Finally, we will explore the molecular mechanisms by which the type-1 interferons influence TR activity. ..
  13. Regulatory T Cell-Deficient Mouse Model Rapidly Develops Sjogren's Syndrome
    Shyr Te Ju; Fiscal Year: 2010
    ..This study should identify new and useful models for Sjogren's syndrome research. It should identify new mechanism(s) for the pathogenesis of the disease and provide potential treatment of the disease. ..
  14. Cytokines in T Regulatory Cell Function
    James W Verbsky; Fiscal Year: 2013
    ..Once we understand how this balance is maintained, therapies can be developed to either strengthen our immunity to treat cancer or infections, or inhibit our immunity to treat autoimmune disease. ..
  15. GBV-C effects on CD4 activation and expansion
    Jack T Stapleton; Fiscal Year: 2012
    ..abstract_text> ..
  16. MECHANISM OF HTLV-I TAX-MEDIATED PHOSPHORYLATION OF IKBA
    EMMETT CUNNINGHAM; Fiscal Year: 2000
    ..The candidate plans ultimately to apply the approaches and techniques learned during the five years of the training program to the study of infectious and immune-mediated eye disease. ..
  17. RENAL CELL CARCINOMA--ADOPTIVE IMMUNOTHERAPY
    KURT STENZEL; Fiscal Year: 1990
    ..Methodology and feasibility for on-line activation of lymphoid cells for adoptive immunotherapy will be investigated using a murine tumor model...
  18. EFFECTS OF PHORBOL ESTERS ON LYMPHOCYTE STIMULATION
    Andrea Mastro; Fiscal Year: 1991
    ..The cells will also be tested for suppressor activity...
  19. INTERLEUKIN REGULATION OF PROOPIOMELANOCORTIN GENE
    S Brown; Fiscal Year: 1990
    ..Finally, we will determine if like CRF, monokines and lymphokines stimulate cAMP generation in pituitary cells. These studies will determine if molecules of divergent origin produce common effects through similar mechanisms...
  20. GROWTH FACTOR RECEPTOR TARGETED TOXINS FOR LEUKEMIA
    John Murphy; Fiscal Year: 1992
    ..It is envisioned that these studies will result in a new class of highly specific and potent biologicals for the treatment of selected leukemias and lymphomas...
  21. IL15 AND NATURAL KILLER (NK) CELL FUNCTION
    William Carson; Fiscal Year: 1999
    ....
  22. The IL-2 receptor in T regulatory cell development
    Thomas R Malek; Fiscal Year: 2012
    ..abstract_text> ..
  23. IMMUNOREGULATION OF ERYTHROPOIESIS
    Lee Levitt; Fiscal Year: 1992
    ..These studies should provide new information in the biology of hematopoietic immunoregulation and are relevant to our understanding of T cell membrane biology and T cell activation...
  24. DEFINITION AND REGULATION OF CELLULAR GENES
    Gary Nabel; Fiscal Year: 1993
    ..The goal of this research is to understand the heterogeneity of kappaB binding proteins, to define cDNAs encoding them, and to selectively inhibit their action on the HIV enhancer without affecting cell viability and function...
  25. DIPHTHERIA TOXIN-RELATED PEPTIDE HORMONE GENE FUSIONS
    John Murphy; Fiscal Year: 1991
    ....
  26. IMMUNOLOGICAL ASPECTS OF RETINOIDS IN HUMAN CANCER
    Neil Sidell; Fiscal Year: 1993
    ..This study will, for the first time in humans, characterize the modulation of antigen-specific immune responses by in vivo administration of a retinoid...
  27. Signaling by a Tyrosine-Deficient IL-2/15 Receptor Beta
    SARAH GAFFEN; Fiscal Year: 2001
    ....
  28. IL2 RECEPTORS--ANALYSIS OF ASSEMBLY AND SIGNALING
    Warner Greene; Fiscal Year: 1999
    ....
  29. TAX PROTEIN OF HTLV-I--MECHANISM OF ACTION AND ROLE
    Peter Kaufman; Fiscal Year: 1991
    ..Together, these studies should lead to a clearer understanding of the mechanism of tax action and its role in HTLV-I induced leukemogenesis...
  30. Anti-Apoptotic Signaling by the IL-2/15 Receptor
    SARAH GAFFEN; Fiscal Year: 2006
    ....
  31. INTERLEUKIN 4 REGULATION OF LYMPHOCYTES
    Mark Boothby; Fiscal Year: 2004
    ..Taken together, the experiments of these Specific Aims will provide new insights into the regulation of the effector and memory-phenotype Th2 subsets. ..
  32. Vector Insertion and Mutagenesis in Human Hematopoiesis
    Christof von Kalle; Fiscal Year: 2007
    ..Results from these studies of insertion sites in the human genome, and the role of LMO2 overexpression on the evolution of a lymphoproliferative phenotype will have great significance for the field. ..
  33. TRANSFORMATION PROPERTIES OF THE HTLV-1 TAX GENE
    RUDY POZZATTI; Fiscal Year: 1992
    ..Once identified these genes will be analyzed to determine what role they may play in the development of a variety of human malignancies. ..
  34. MECHANISM OF INTERLEUKIN 1 ACTION
    STEVEN MIZEL; Fiscal Year: 1993
    ....
  35. CYTOKINE INDUCIBLE GENES IN HEMATOPOIESIS
    Yu Chung Yang; Fiscal Year: 2002
    ....
  36. DESIGN OF MULTIMERIC INTERLEUKIN-2 RECEPTOR ECTODOMAINS
    Thomas Ciardelli; Fiscal Year: 2000
    ..4. To obtain detailed structure-activity data on these complexes by co-crystallizing them with IL-2 and determining their X-ray structures to high resolution. ..
  37. Zinc Deficiency and Thl Functions: Molecular Mechanisms
    Ananda Prasad; Fiscal Year: 2006
    ..For this study we will select appropriate number of healthy ambulatory elderly subjects from a nursing home. Our previous experience indicates that approximately 30 percent of these healthy elderly are zinc deficient. ..
  38. NCI CLINICAL INVESTIGATOR AWARD
    David Peace; Fiscal Year: 1991
    ....
  39. Biologic therapy of Melanoma and Renal Cell Cancer
    Michael Atkins; Fiscal Year: 2006
    ..abstract_text> ..
  40. SUPPRESSION OF T CELL ACTIVATION BY DIETARY FATTY ACIDS
    ROBERT CHAPKIN; Fiscal Year: 2003
    ..g., rheumatoid arthritis), without compromising host defenses. ..
  41. MOLECULAR PATHOGENESIS OF PLASMA CELL NEOPLASMS
    PETER BERGSAGEL; Fiscal Year: 2001
    ....
  42. XRAY STUDIES OF EPO AND IL2 RECEPTOR COMPLEXES
    Ian Wilson; Fiscal Year: 2001
    ..The crystallographic study of IL-2 mutants and various forms of the receptor complex should give insights into the structure and function of this key receptor in T cell growth and proliferation. ..
  43. INFLAMMATION MARKERS OVER TIME IN CARDIOVASCULAR DISEASE
    Russell Tracy; Fiscal Year: 2002
    ..It is likely our results will have important implications for prevention, diagnosis, and future therapeutic interventions in cardiovascular disease in the elderly. ..
  44. REGULATION OF PERIPHERAL T CELL SURVIVAL BY INTERLEUKIN-
    DENNIS WILLERFORD; Fiscal Year: 2000
    ..Hence these studies are directly relevant to the pathogenesis of autoimmune diseases, lymphoid cancers and AIDS. ..
  45. PREDICTIVE VALUE OF SURROGATE SERUM MARKERS AZT THERAPY
    Mohan Reddy; Fiscal Year: 1990
    ....
  46. IL-2 GENE DELETION: NEURODEVELOPMENT AND BEHAVIOR
    JOHN PETITTO; Fiscal Year: 2002
    ..We believe that the proposed research is timely and will lay an essential foundation on which to build in future studies. ..
  47. Regulation of Th1 responses by IL-2 receptor blockade
    John McDyer; Fiscal Year: 2007
    ..This K08 will provide the foundation for a research career dedicated to translational studies in immunology. ..
  48. Phase-I-II Study of DAB389 (ONTAK) in Patients with Adv. Refractory Breast Cancer
    Lupe Salazar; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  49. REGULATORY MECHANISMS IN HUMAN NATURAL CYTOTOXICITY
    Takashi Makinodan; Fiscal Year: 1990
    ..Methodologies involving cell isolation and mixture techniques, use of monoclonal and polyclonal reagents, receptor-ligand binding studies, and analyses of protein and mRNA synthesis are proposed...
  50. REGULATION OF C-FOS EXPRESSION DURING T CELL ACTIVATION
    Stephen Benedict; Fiscal Year: 1992
    ..We will determine the size, complexity, and potential activating or inactivating modifications of some of the c-fos DNA binding complexes...
  51. Therapeutic immune mechanisms of daclizumab in psoriasis
    James Krueger; Fiscal Year: 2004
    ..We will also measure the impact of daclizumab on T cell activation/deviation towards Type 2 T cells by sensitive flow cytometry based assays. ..
  52. THRESHOLD CONTROL FOR T CELL ANTIGEN RECEPTOR
    Makio Iwashima; Fiscal Year: 2004
    ..This will provide key information to understand the etiology of autoimmune diseases and its prevention and treatment and will contribute to establish the procedure to provoke anti-cancer immune responses. ..
  53. THRESHOLD CONTROL FOR T CELL ANTIGEN RECEPTOR
    Makio Iwashima; Fiscal Year: 2005
    ....
  54. MODULATION OF AIRWAY INFLAMMATION IN ASTHMA MODELS
    David Center; Fiscal Year: 2000
    ..These studies are designed to: (1) define the conditions in the sensitization phase required to induce epithelial cell-derived IL-16; and (2) to determine the mechanism for IL-16's effect on IgE antibody production. ..
  55. ROLE OF IL2 RECEPTOR POSITIVE CELLS IN TRANSPLANTATION
    Nicholas Tilney; Fiscal Year: 1991
    ..Their modulation by specific therapies may be critical in clinical transplantation...
  56. SAR OF INTERLEUKIN 2 AND IL-2 RELATED PEPTIDES
    Thomas Ciardelli; Fiscal Year: 1993
    ....
  57. Signaling of IL-2Rgamma Cytokines
    Yu Chung Yang; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  58. PATHOLOGY AND IMMUNOCYTOLOGY OF THE OLIGODENDROCYTE
    George Moore; Fiscal Year: 1992
    ..This information might be relevant to future therapeutic protocols in this disease...
  59. SCHIZOPHRENIA AND IMMUNE ACTIVATION
    Mark Rapaport; Fiscal Year: 2001
    ..These findings would be important because they would allow us to biologically subtype a group of schizophrenic patients. ..
  60. Improved Humanized Mouse Models for Vaccine Development
    Donald Mosier; Fiscal Year: 2009
    ..After many years of work, that goal seems close. This proposal will attempt to fix the few remaining problems in "humanized mice", and use them to test a new AIDS vaccine decorated with sugar groups from the virus. ..
  61. Immunological Monitoring of Heart Allograft Recipients
    Nicole Suciu Foca; Fiscal Year: 2006
    ....
  62. MECHANISM OF T CELL ANERGY INDUCED BY BREAST CANCER
    ALAN FREY; Fiscal Year: 2003
    ..The proposed research shall test the hypothesis that the tumor microenvironment induces the activity of an mRNA binding factor in TIL that stabilizes IL-2 mRNA and sequesters it unable to be translated. ..
  63. IL-2 LIPSOMES AS DELIVERY AGENTS FOR IMMUNOTHERAPEUTICS
    PAULA KONIGSBERG; Fiscal Year: 1991
    ..The commercial objective is to develop a liposomal product which targets an antiproliferative drug to unwanted cells of the immune system while minimizing the toxicity that is currently associated with the free drug...