Ethan M Shevach

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Regulatory T cells. Introduction
    E M Shevach
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH Building 10, Room 11N315, 10 Center Drive, Bethesda, MD 20892 1892, USA
    Semin Immunol 16:69-71. 2004
  2. pmc CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness
    Ciriaco A Piccirillo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    J Exp Med 196:237-46. 2002
  3. pmc CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner
    John Andersson
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 205:1975-81. 2008
  4. pmc Application of IL-2 therapy to target T regulatory cell function
    Ethan M Shevach
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Immunol 33:626-32. 2012
  5. ncbi request reprint From vanilla to 28 flavors: multiple varieties of T regulatory cells
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 25:195-201. 2006
  6. ncbi request reprint The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells
    Ethan M Shevach
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Immunol Rev 212:60-73. 2006
  7. ncbi request reprint The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity?
    Ethan M Shevach
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 6:613-8. 2006
  8. pmc Special regulatory T cell review: How I became a T suppressor/regulatory cell maven
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunology 123:3-5. 2008
  9. pmc The critical contribution of TGF-beta to the induction of Foxp3 expression and regulatory T cell function
    Ethan M Shevach
    Laboratory of Immunology, NIAID, NIH, Bethesda, MD 20892, USA
    Eur J Immunol 38:915-7. 2008
  10. ncbi request reprint CD4+ CD25+ suppressor T cells: more questions than answers
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 2:389-400. 2002

Detail Information

Publications97

  1. ncbi request reprint Regulatory T cells. Introduction
    E M Shevach
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH Building 10, Room 11N315, 10 Center Drive, Bethesda, MD 20892 1892, USA
    Semin Immunol 16:69-71. 2004
  2. pmc CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness
    Ciriaco A Piccirillo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    J Exp Med 196:237-46. 2002
    ..Collectively, these results demonstrate that CD4(+)CD25(+) suppressor function can occur independently of TGF-beta1...
  3. pmc CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner
    John Andersson
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 205:1975-81. 2008
    ..T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities...
  4. pmc Application of IL-2 therapy to target T regulatory cell function
    Ethan M Shevach
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Immunol 33:626-32. 2012
    ....
  5. ncbi request reprint From vanilla to 28 flavors: multiple varieties of T regulatory cells
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 25:195-201. 2006
    ..Shevach discusses the current understanding of the different subsets of T regulatory cells and provides a perspective on the current areas of uncertainly and controversy in the field...
  6. ncbi request reprint The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells
    Ethan M Shevach
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Immunol Rev 212:60-73. 2006
    ..Natural Treg-mediated killing of antigen-presenting cells may represent one pathway by which they can induce long-lasting suppression of autoimmune disease...
  7. ncbi request reprint The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity?
    Ethan M Shevach
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 6:613-8. 2006
    ..Here we propose a model in which GITR-GITR-ligand interactions co-stimulate both responder T-cell functions and the suppressive functions of T(Reg) cells...
  8. pmc Special regulatory T cell review: How I became a T suppressor/regulatory cell maven
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunology 123:3-5. 2008
    ..I am optimistic that manipulation of regulatory T-cell function will shortly be applicable to the clinic...
  9. pmc The critical contribution of TGF-beta to the induction of Foxp3 expression and regulatory T cell function
    Ethan M Shevach
    Laboratory of Immunology, NIAID, NIH, Bethesda, MD 20892, USA
    Eur J Immunol 38:915-7. 2008
    ..TGF-beta expressed on the surface of Treg also induces Foxp3 expression and Treg function in responder cells. Both of these mechanisms may play a role in vivo in the induction of antigen-specific extra-thymic Treg...
  10. ncbi request reprint CD4+ CD25+ suppressor T cells: more questions than answers
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 2:389-400. 2002
    ....
  11. doi request reprint Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Blg 10, Room 11N315, Bethesda, MD 20892, USA
    J Clin Immunol 28:640-6. 2008
    ..Coculture of activated Treg with naive responder T cells results in the de novo generation of fully functional Foxp3(+) T cells in a contact-dependent and TGF-beta-dependent manner...
  12. doi request reprint Immunology. Regulating suppression
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 322:202-3. 2008
  13. doi request reprint Mechanisms of foxp3+ T regulatory cell-mediated suppression
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 30:636-45. 2009
    ..An increase in our understanding of Treg cell suppressor mechanisms will offer an insight into how Treg cell function can be manipulated either positively or negatively in vivo...
  14. pmc Cutting edge: antigen-specific TGF beta-induced regulatory T cells suppress Th17-mediated autoimmune disease
    Eva N Huter
    Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:8209-13. 2008
    ..Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed...
  15. doi request reprint Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells
    Eva N Huter
    Laboratory of Immunology, Cellular Immunology Section, NIAID, NIH, Bethesda, MD, USA
    Int Immunopharmacol 9:540-5. 2009
    ..Thus, antigen-specific iTreg are potent suppressors of autoimmune gastritis induced by both, fully differentiated Th1 and Th17 effector cells...
  16. 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...
  17. ncbi request reprint CD4+CD25+ regulatory T cells are activated in vivo by recognition of self
    John Andersson
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, 10 Center Drive, MSC 1892, Bethesda, MD 20892 1892, USA
    Int Immunol 19:557-66. 2007
    ..Thus, a sub-population of nT(R) is activated by recognition of self-peptide-MHC class II ligands in vivo, resulting in their capacity to be induced to mediate suppressor function in vitro in the absence of TCR stimulation...
  18. pmc Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells
    Georg H Stummvoll
    Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:1908-16. 2008
    ....
  19. ncbi request reprint Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells
    Geoffrey L Stephens
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 173:5008-20. 2004
    ..The down-regulation of GITR-L by inflammatory stimuli may enhance the susceptibility of effector T cells to suppressor activity during the course of an infectious insult...
  20. pmc Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway
    Kevin M Elias
    Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD, USA
    Blood 111:1013-20. 2008
    ....
  21. ncbi request reprint Autoantigen-specific TGFbeta-induced Foxp3+ regulatory T cells prevent autoimmunity by inhibiting dendritic cells from activating autoreactive T cells
    Richard J DiPaolo
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Immunol 179:4685-93. 2007
    ..These studies reveal the therapeutic potential of Ag specific iTregs to prevent autoimmunity, and provide a mechanism by which this population of regulatory T cells, and perhaps others, mediate their suppressive effects in vivo...
  22. ncbi request reprint A novel protective model against experimental allergic encephalomyelitis in mice expressing a transgenic TCR-specific for myelin oligodendrocyte glycoprotein
    Itzhak Mendel
    Laboratory of Immunology, Cellular Immunology Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N315, 10 Center Drive, Bethesda, MD 20892 1892, USA
    J Neuroimmunol 149:10-21. 2004
    ..The unique phenotype of these autoantigen-specific T cells may represent an important mechanism of protection against autoimmune disease...
  23. ncbi request reprint 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...
  24. pmc T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance
    Marko Pesu
    Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 455:246-50. 2008
    ..Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance...
  25. pmc IL-2 controls the stability of Foxp3 expression in TGF-beta-induced Foxp3+ T cells in vivo
    Qian Chen
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 186:6329-37. 2011
    ..Administration of IL-2 in vivo results in stabilization of Foxp3 expression and may prove to be a valuable adjunct for the use of iTreg for the treatment of autoimmune diseases...
  26. pmc Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling
    Kamran Ghoreschi
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 467:967-71. 2010
    ..These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications...
  27. ncbi request reprint Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation
    Arian Laurence
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 26:371-81. 2007
    ..We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2...
  28. pmc Transforming growth factor-beta1 enhances the interferon-gamma-dependent, interleukin-12-independent pathway of T helper 1 cell differentiation
    Ronald B Smeltz
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunology 114:484-92. 2005
    ..These data have important implications for strategies being considered for the use of TGF-beta-producing T cells for the treatment of autoimmune disorders...
  29. ncbi request reprint Activation requirements for the induction of CD4+CD25+ T cell suppressor function
    Angela M Thornton
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20892 1892, USA
    Eur J Immunol 34:366-76. 2004
    ..These studies support the view that activation of CD25(+) T cells requires IL-2/IL-4 for their survival/differentiation into effector cells, but is independent of CD28/CTLA-4-mediated costimulation...
  30. ncbi request reprint Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice
    Sophie Candon
    Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
    J Immunol 172:2917-24. 2004
    ..This in vivo model of spontaneous Th2-mediated, organ-specific autoimmunity provides a unique example in which the clonotypic TCR conveys the Th2 disease phenotype...
  31. pmc Activated T cells express the OX40 ligand: requirements for induction and costimulatory function
    Itzhak Mendel
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunology 117:196-204. 2006
    ....
  32. ncbi request reprint Bone marrow-derived dendritic cells reverse the anergic state of CD4+CD25+ T cells without reversing their suppressive function
    Carine Brinster
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 175:7332-40. 2005
    ..Collectively, these results suggest that Ag presentation by DC can induce the expansion of CD4+CD25+ T cells while simultaneously activating their ability to suppress cytokine secretion by effector T cells...
  33. ncbi request reprint The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells
    Matthias Hesse
    Laboratories of Parasitic Diseases and Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:3157-66. 2004
    ..Thus, innate effectors and regulatory T cells producing IL-10 cooperate to reduce morbidity and prolong survival in schistosomiasis...
  34. pmc CD4+ CD25+ [corrected] regulatory T cells render naive CD4+ CD25- T cells anergic and suppressive
    Miao Qiao
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    Immunology 120:447-55. 2007
    ..Therefore nTreg are not only able to suppress immune responses by inhibiting cytokine production by CD4(+) CD25(-) responder cells, but also appear to modulate the responder cells to render them both anergic and suppressive...
  35. pmc Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103+ inducible regulatory T cells
    Jinfang Zhu
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 206:329-41. 2009
    ..Thus, Gfi-1 plays a critical role both in enhancing Th2 cell expansion and in repressing induction of Th17 and CD103(+) iTreg cells...
  36. pmc The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases
    Francoise Meylan
    Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
    Immunity 29:79-89. 2008
    ..DR3 could be an attractive therapeutic target for T cell-mediated autoimmune and allergic diseases...
  37. pmc Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism
    Gouri Chattopadhyay
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
    J Immunol 191:5875-84. 2013
    ..Taken together, these studies demonstrate that a major suppressive mechanism of DC function by iTregs is secondary to the effects of IL-10 on MARCH1 and CD83 expression. ..
  38. ncbi request reprint The IL-10-producing competence of Th2 cells generated in vitro is IL-4 dependent
    Itzhak Mendel
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
    Eur J Immunol 32:3216-24. 2002
    ..Collectively, our results raise doubts about the existence of a unique population of CD4+ regulatory T cells that can be generated by activation in the presence of IL-10...
  39. ncbi request reprint TGF-beta1 production by CD4+ CD25+ regulatory T cells is not essential for suppression of intestinal inflammation
    Marika C Kullberg
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Eur J Immunol 35:2886-95. 2005
    ....
  40. pmc Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function
    Dat Q Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 182:2929-38. 2009
    ..Taken together, one of the mechanisms of Treg-mediated suppression functions across species and mediates an LFA-1/ICAM-1-dependent interaction between Tregs and DCs...
  41. ncbi request reprint Distinct subsets of FoxP3+ regulatory T cells participate in the control of immune responses
    Geoffrey L Stephens
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 178:6901-11. 2007
    ..Effector FoxP3(+) T cells may act as a sentinel of tolerance, providing a first line of defense against potentially harmful responses by rapidly suppressing immunity to peripheral self-Ags...
  42. pmc Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype
    Dat Q Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 110:2983-90. 2007
    ..These results suggest that even high levels of FOXP3 expression are insufficient to define a human CD4+ T cell as a T-regulatory cell...
  43. pmc Activated CD4+CD25+ T cells selectively kill B lymphocytes
    Dong Mei Zhao
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg 10, Rm 11N315, Bethesda, MD 20892, USA
    Blood 107:3925-32. 2006
    ..Our results demonstrate that CD4+CD25+ T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+ T cells can be explained, at least in part, by the direct regulation of B-cell function...
  44. ncbi request reprint Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease
    Rebecca S McHugh
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:5979-83. 2002
    ..These results demonstrate that second signals (nonspecific proliferation, TCR activation, or inflammation) are needed for induction of autoimmunity in the absence of CD25(+) regulatory T cells...
  45. ncbi request reprint Control of T cell activation by CD4+CD25+ suppressor T cells
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    Novartis Found Symp 252:24-36; discussion 36-44, 106-14. 2003
    ..Multiple methods of manipulating both the numbers of CD4+CD25+ suppressor T cells and their activation status are now available and will rapidly be applied to therapy of autoimmune, infectious and malignant diseases...
  46. pmc Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival
    Qian Chen
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 183:4458-66. 2009
    ..Development of methods to selectively stimulate TLR2 on Treg may lead to a novel approaches for the treatment of autoimmune diseases...
  47. ncbi request reprint Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression
    Ronald B Smeltz
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:6165-72. 2002
    ..These data clarify the role of IFN-gamma in regulation of IL-18Ralpha/IL-12Rbeta2 during both IL-12-dependent and IL-12-independent Th1 differentiation...
  48. ncbi request reprint CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells
    Richard J DiPaolo
    Section of Cellular Immunology, Laboratory of Immunology, National Institutes of Health, Bethesda, MD 20892 1892, USA
    J Immunol 175:7135-42. 2005
    ..The primary effect of nTreg appeared to be inhibition of differentiation of autoantigen-specific T cells to Th1 effector cells, as reflected by a decrease in Ag-stimulated IFN-gamma production and a reduction in T-bet expression...
  49. ncbi request reprint Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells
    Todd S Davidson
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 178:4022-6. 2007
    ..As TGF-beta-induced T regulatory cells can be easily grown in vitro, they may prove useful for the treatment of autoimmune diseases, for the prevention of graft rejection, and graft versus host disease...
  50. pmc Autoantibodies in scurfy mice and IPEX patients recognize keratin 14
    Eva N Huter
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    J Invest Dermatol 130:1391-9. 2010
    ..Thus, the results of our study indicate that autoantibodies in Scurfy mice and patients with IPEX target keratins...
  51. pmc Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation
    Justin P Edwards
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
    J Immunol 190:5506-15. 2013
    ..Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-β1/GARP complex on their cell surface rather than by secreted latent TGF-β1...
  52. doi request reprint Modulation of Treg cells/T effector function by GITR signaling is context-dependent
    Amal Ephrem
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Eur J Immunol 43:2421-9. 2013
    ..The effects of GITR activation are complex and depend on the host environment and the activation state of the Treg cells and T effector cells. ..
  53. doi request reprint Biological functions of regulatory T cells
    Ethan M Shevach
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Adv Immunol 112:137-76. 2011
    ..A complete understand of the biological functions of Tregs in vivo should facilitate the development of pharmacologic and biologic agents that can be used to modulate Treg function in a therapeutic setting...
  54. pmc TGF-beta-induced Foxp3+ regulatory T cells rescue scurfy mice
    Eva N Huter
    Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Eur J Immunol 38:1814-21. 2008
    ..Thus, TGF-beta-differentiated Foxp3+ Treg appear to possess all of the functional properties of thymic-derived nTreg and represent a potent population for the cellular immunotherapy of autoimmune and inflammatory diseases...
  55. pmc GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells
    Dat Q Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:13445-50. 2009
    ..Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism...
  56. ncbi request reprint Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function
    Angela M Thornton
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:6519-23. 2004
    ....
  57. ncbi request reprint The role of suppressor T cells in regulation of immune responses
    Rebecca S McHugh
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Allergy Clin Immunol 110:693-702. 2002
    ..Therefore immunologic or pharmacologic manipulation of regulatory T-cell populations represents an important future approach to immunotherapy of a wide range of immune responses...
  58. pmc Costimulatory effects of IL-1 on the expansion/differentiation of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3- T cells
    Carine Brinster
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA
    J Leukoc Biol 84:480-7. 2008
    ..These findings have important implications for the design of protocols for the expansion of CD4+CD25+ T cells for cellular biotherapy...
  59. ncbi request reprint 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
    ....
  60. pmc Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures
    Dat Q Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 113:5125-33. 2009
    ..This novel protocol should facilitate the purification of Tregs for both cell-based therapies as well as detailed studies of human Treg function in health and disease...
  61. pmc Polyclonal Treg cells modulate T effector cell trafficking
    Todd S Davidson
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Eur J Immunol 41:2862-70. 2011
    ....
  62. pmc In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIV-infected patients
    Irini Sereti
    National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
    J Clin Invest 115:1839-47. 2005
    ..These CD4CD25 cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4 T cell pool...
  63. ncbi request reprint Differentiated Th1 autoreactive effector cells can induce experimental autoimmune encephalomyelitis in the absence of IL-12 and CD40/CD40L interactions
    Itzhak Mendel
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, 10 11N307, 10 Center Drive MSC 1892, Bethesda, MD 20892 1892, USA
    J Neuroimmunol 122:65-73. 2002
    ..These results have important implications regarding the therapeutic usefulness of blockade of IL-12 or the CD40/CD40L pathway for treatment of autoimmune disease...
  64. pmc Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion
    Yong Chan Kim
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 119:2810-8. 2012
    ....
  65. doi request reprint Therapeutic potential of FOXP3(+) regulatory T cells and their interactions with dendritic cells
    Dat Q Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Hum Immunol 70:294-9. 2009
    ..This review will focus on their therapeutic potential and mechanisms of action, particularly their interaction with dendritic cells...
  66. pmc Regulatory T-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens
    George A Punkosdy
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 108:3677-82. 2011
    ..Thus, one unique mechanism by which certain infectious agents evade host immune responses may be mediated by endogenous Sag-dependent activation and expansion of Treg...
  67. 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...
  68. pmc TNF downmodulates the function of human CD4+CD25hi T-regulatory cells
    Xavier Valencia
    Autoimmunity Branch, the Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institute of Health NIAMS NIH, Bethesda, MD 20892, USA
    Blood 108:253-61. 2006
    ..Thus, TNF has a novel action in modulating autoimmunity, by inhibiting CD4+CD25+ Treg activity...
  69. ncbi request reprint Regulatory T cells in autoimmmunity*
    E M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Immunol 18:423-49. 2000
    ..Conversely, enhancement of regulatory T cell function may be a useful adjunct to the therapy of autoimmune diseases and for prevention of allograft rejection...
  70. ncbi request reprint Control of T-cell activation by CD4+ CD25+ suppressor T cells
    E M Shevach
    Cellular Immunology Section, Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Immunol Rev 182:58-67. 2001
    ....
  71. ncbi request reprint A T cell receptor transgenic model of severe, spontaneous organ-specific autoimmunity
    R S McHugh
    Cellular Immunology Section, Laboratory of Immunology, NIAID, NIH, Bethesda, MD, USA
    Eur J Immunol 31:2094-103. 2001
    ....
  72. ncbi request reprint Control of organ-specific autoimmunity by immunoregulatory CD4(+)CD25(+) T cells
    R S McHugh
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Microbes Infect 3:919-27. 2001
    ..In vitro model systems have been developed to study the function of these potent suppressor cells. Following their activation via their T-cell receptor, they downregulate the responses of CD25(-) effectors by a T-T interaction...
  73. pmc Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor-beta signal transduction
    Yong Chan Kim
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunology 130:484-93. 2010
    ..Our results suggest that one mechanism responsible for the immunosuppressive effects of statins is the ability to promote the generation of Foxp3(+) T regulatory cells...
  74. ncbi request reprint Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells
    C A Piccirillo
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 167:1137-40. 2001
    ....
  75. pmc Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node
    Clemens Scheinecker
    Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases NIAID, National Institutes of Health NIH, Bethesda, MD 20892, USA
    J Exp Med 196:1079-90. 2002
    ....
  76. ncbi request reprint Antigen-independent, integrin-mediated T cell activation
    K Sturmhöfel
    Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
    J Immunol 154:2104-11. 1995
    ..Such integrin-mediated, Ag-independent activation of T cells may play a critical role in the potentiation of inflammatory responses...
  77. pmc The mouse vitronectin receptor is a T cell activation antigen
    K Moulder
    Biological Resources Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
    J Exp Med 173:343-7. 1991
    ..In view of recent studies demonstrating that this molecule functions as an accessory molecule in T cell activation, the VNR may play an important role in mouse T cell functions...
  78. ncbi request reprint Characterization of a cell surface-expressed disulfide-linked dimer involved in murine T cell activation
    W M Yokoyama
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
    J Immunol 141:369-76. 1988
    ..These functional and biochemical studies strongly suggest that the Ag recognized by H1.2F3 is the murine homologue of the human CD28 Ag recognized by mAb 9.3...
  79. pmc Regulation of interleukin (IL)-18 receptor alpha chain expression on CD4(+) T cells during T helper (Th)1/Th2 differentiation. Critical downregulatory role of IL-4
    R B Smeltz
    Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 194:143-53. 2001
    ..Thus, positive/negative regulation of the IL-18Ralpha by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response...
  80. ncbi request reprint A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis
    R Ortmann
    Laboratories of Immunology and Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 166:5712-9. 2001
    ..This subtle abnormality in IL-12 responsiveness results in a profound defect in the generation of Th1 cells and the development of autoimmune disease...
  81. ncbi request reprint Mouse autoreactive gamma/delta T cells. II. Molecular characterization of the T cell receptor
    A Ezquerra
    Biological Resources Branch, National Institute of Allergy and Infectious Diseases, National Instiutes of Health, Bethesda, MD 20892
    Eur J Immunol 22:491-8. 1992
    ....
  82. pmc Inhibition of the function of the FcgammaRIIB by a monoclonal antibody to thymic shared antigen-1, a Ly-6 family antigen
    L Ding
    Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20851 1448, USA
    Immunology 104:28-36. 2001
    ....
  83. ncbi request reprint Spatial genome organization during T-cell differentiation
    S H Kim
    National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Cytogenet Genome Res 105:292-301. 2004
    ..Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex...
  84. ncbi request reprint A murine T lymphocyte antigen belongs to a supergene family of type II integral membrane proteins
    W M Yokoyama
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892
    J Immunol 143:1379-86. 1989
    ....
  85. ncbi request reprint Role of costimulation in the induction of the IL-12/IL-12 receptor pathway and the development of autoimmunity
    J T Chang
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    J Immunol 164:100-6. 2000
    ..These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity...
  86. pmc Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous IL-12: a critical step in the differentiation of pathogenic autoreactive T cells
    J T Chang
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Exp Med 189:969-78. 1999
    ..These results suggest that the development of immunotherapies that target the IL-12Rbeta2 subunit may be useful for the treatment of autoimmune diseases...
  87. pmc An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease
    B M Segal
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Exp Med 187:537-46. 1998
    ..This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease...
  88. ncbi request reprint Engagement of the vitronectin receptor (alpha V beta 3) on murine T cells stimulates tyrosine phosphorylation of a 115-kDa protein
    C Brando
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
    J Immunol 154:2005-11. 1995
    ..This result raises the possibility that induction of pp115 is a common biochemical step in signal transduction by both the TCR and the VNR...
  89. ncbi request reprint Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance
    Ciriaco A Piccirillo
    Department of Microbiology and Immunology, Host Resistance Laboratory, McGill University, Montreal, Que, Canada H3A 2B4
    Semin Immunol 16:81-8. 2004
    ..We propose the existence of two general subsets of CD4(+)CD25(+) Treg cells, naturally-occurring and induced, that differ in their origin, developmental and activation requirements, and mechanism of action...
  90. ncbi request reprint Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy
    Helen Y Wang
    The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Immunity 20:107-18. 2004
    ..These findings suggest that the presence of tumor-specific CD4(+) Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer...
  91. ncbi request reprint Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells
    Helen Y Wang
    Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    J Immunol 174:2661-70. 2005
    ....
  92. ncbi request reprint Promiscuous thymic expression of an autoantigen gene does not result in negative selection of pathogenic T cells
    Stacey Allen
    Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
    J Immunol 175:5759-64. 2005
    ..This work, taken together with our previous studies, highlights that thymic autoantigen expression does not necessarily result in the induction of tolerance...
  93. ncbi request reprint Regulatory/suppressor T cells in health and disease
    Ethan M Shevach
    Arthritis Rheum 50:2721-4. 2004
  94. ncbi request reprint Cutting Edge: IL-10-producing CD4+ T cells mediate tumor rejection
    Benjamin M Segal
    Department of Neurology, The Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    J Immunol 168:1-4. 2002
    ..Hence, our findings demonstrate that IL-10-producing CD4+ T cells can manifest antitumor functions and suggest that IL-10 may have proinflammatory effects in disease states...
  95. ncbi request reprint Fatal attraction: tumors beckon regulatory T cells
    Ethan M Shevach
    Nat Med 10:900-1. 2004
  96. ncbi request reprint What does the future hold for cell-based tolerogenic therapy?
    Jeffrey A Bluestone
    Immune Tolerance Network and of the Diabetes Center at the University of California, USA
    Nat Rev Immunol 7:650-4. 2007
    ....
  97. pmc CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence
    Ekaterina Yurchenko
    Department of Microbiology and Immunology, McGill University, Montreal, H3A 2B4, Canada
    J Exp Med 203:2451-60. 2006
    ..Thus, this study shows that CCR5 directs the homing of CD4+CD25+ nTreg cells to L. major-infected dermal sites where they promote the establishment of infection and long-term survival of the parasite in the immune host...