S Sakaguchi

Summary

Affiliation: Kyoto University
Country: Japan

Publications

  1. ncbi request reprint Animal models of arthritis caused by systemic alteration of the immune system
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Curr Opin Immunol 17:589-94. 2005
  2. pmc Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model
    Keiji Hirota
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 204:2803-12. 2007
  3. 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
  4. pmc Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells
    Kuibeom Ko
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    J Exp Med 202:885-91. 2005
  5. pmc Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization
    Ruka Setoguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 201:723-35. 2005
  6. pmc A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice
    Hiroyuki Yoshitomi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Exp Med 201:949-60. 2005
  7. pmc Chronic arthritis leads to disturbances in the bone collagen network
    Joana Caetano-Lopes
    Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649 028 Lisbon, Portugal
    Arthritis Res Ther 12:R9. 2010
  8. doi request reprint Regulatory T cells in the past and for the future
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Eur J Immunol 38:901-37. 2008
  9. ncbi request reprint 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
  10. doi request reprint FOXP3+ regulatory T cells in the human immune system
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Nat Rev Immunol 10:490-500. 2010

Detail Information

Publications96

  1. ncbi request reprint Animal models of arthritis caused by systemic alteration of the immune system
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Curr Opin Immunol 17:589-94. 2005
    ..In particular, they now provide insights into how systemic alterations of the immune system result in a local development of chronic arthritis that leads to joint destruction...
  2. pmc Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model
    Keiji Hirota
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 204:2803-12. 2007
    ..These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA...
  3. 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...
  4. pmc Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells
    Kuibeom Ko
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    J Exp Med 202:885-91. 2005
    ..Agonistic anti-GITR mAb is therefore instrumental in treating advanced cancers...
  5. pmc Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization
    Ruka Setoguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 201:723-35. 2005
    ..Furthermore, impairment of this negative feedback loop via IL-2 can be a cause and a predisposing factor for autoimmune disease...
  6. pmc A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice
    Hiroyuki Yoshitomi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Exp Med 201:949-60. 2005
    ....
  7. pmc Chronic arthritis leads to disturbances in the bone collagen network
    Joana Caetano-Lopes
    Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649 028 Lisbon, Portugal
    Arthritis Res Ther 12:R9. 2010
    ..In this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by chronic inflammation is associated with an imbalance in bone turnover and also a disorganization of the bone type I collagen network...
  8. doi request reprint Regulatory T cells in the past and for the future
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Eur J Immunol 38:901-37. 2008
  9. ncbi request reprint 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
    ....
  10. doi request reprint FOXP3+ regulatory T cells in the human immune system
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Nat Rev Immunol 10:490-500. 2010
    ..We discuss future studies that are needed for the successful therapeutic use of human T(Reg) cells...
  11. doi request reprint Regulatory T cells: how do they suppress immune responses?
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo ku, Kyoto, Japan
    Int Immunol 21:1105-11. 2009
    ..These findings will help to design effective ways for controlling immune responses by targeting Treg suppressive functions...
  12. ncbi request reprint 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...
  13. ncbi request reprint Regulatory T cells in immunologic self-tolerance and autoimmune disease
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Kyoto, Japan
    Int Rev Immunol 24:211-26. 2005
    ..This regulatory population can be exploited to prevent and treat autoimmune disease by strengthening and reestablishing immunologic self-tolerance...
  14. ncbi request reprint Regulatory T cells
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto, 606 8507, Japan
    Springer Semin Immunopathol 28:1-2. 2006
  15. ncbi request reprint Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Semin Immunol 18:199-206. 2006
    ..This model is instrumental in understanding how genetic variations in T cell signal transduction, together with environmental influences, contribute to the development of autoimmune disease...
  16. ncbi request reprint Dynamics of peripheral tolerance and immune regulation mediated by Treg
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Eur J Immunol 39:2331-6. 2009
    ..These dynamics provide ample opportunities for immune intervention for the benefit of the host...
  17. ncbi request reprint Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Immunol Rev 212:8-27. 2006
    ....
  18. ncbi request reprint Regulatory T cells - a brief history and perspective
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Eur J Immunol 37:S116-23. 2007
    ..They can be exploited for clinical use to treat immunological diseases and control physiological and pathological immune responses...
  19. doi request reprint Regulatory T cells and immune tolerance
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Cell 133:775-87. 2008
    ..Recent research reveals the cellular and molecular basis of Treg development and function and implicates dysregulation of Tregs in immunological disease...
  20. ncbi request reprint Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease
    S Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    Curr Top Microbiol Immunol 305:51-66. 2006
    ..Genetically determined or environmentally induced abnormality in CD25+CD4+ regulatory T cell development, maintenance, and function can be a cause of autoimmune disease in humans...
  21. ncbi request reprint Immunologic tolerance maintained by regulatory T cells: implications for autoimmunity, tumor immunity and transplantation tolerance
    Shimon Sakaguchi
    Dep Exp Pathol, Inst Frontier Med Sci, Kyoto Univ, Kyoto, Japan
    Vox Sang 83:151-3. 2002
  22. ncbi request reprint Animal models of autoimmunity and their relevance to human diseases
    S Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Curr Opin Immunol 12:684-90. 2000
    ..There is, for example, accumulating evidence that elimination or dysfunction of regulatory T cells can elicit T cell mediated, destructive autoimmune disease in otherwise normal animals and enhance autoimmunity in spontaneous models...
  23. pmc The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    J Clin Invest 112:1310-2. 2003
    ..Genetic defects in FOXP3 cause IPEX, an X-linked autoimmune/inflammatory syndrome. With FOXP3 as a specific marker for regulatory CD4+ T cells in humans, it is now possible to determine their origin and developmental pathway...
  24. ncbi request reprint Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity
    S Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin Kawaharacho 53, Sakyo ku, Kyoto 606 8507, Japan
    Microbes Infect 3:911-8. 2001
    ..Abrogation of the control can evoke potent tumor immunity as well as autoimmunity in normal animals. This common regulatory mechanism for autoimmunity and tumor immunity can be exploited to devise a novel immunotherapy against cancer...
  25. pmc Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 197:397-401. 2003
  26. ncbi request reprint 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...
  27. ncbi request reprint Naturally arising CD25+CD4+ regulatory T cells in tumor immunity
    T Nomura
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Curr Top Microbiol Immunol 293:287-302. 2005
    ..This common regulatory mechanism for autoimmunity and tumor immunity can be exploited when devising a novel immunotherapy for cancer...
  28. ncbi request reprint [Regulatory T cells]
    Takatoku Oida
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
    Nihon Rinsho 63:154-8. 2005
  29. pmc Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice
    Hiroshi Hata
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    J Clin Invest 114:582-8. 2004
    ..The results also indicate that targeting not only each cytokine but also each cell population secreting distinct cytokines could be an effective treatment of rheumatoid arthritis...
  30. ncbi request reprint Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells
    Eiji Nishimura
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Faculty of Medicine, Kyoto University, Japan
    Int Immunol 16:1189-201. 2004
    ....
  31. pmc T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis
    Keiji Hirota
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 204:41-7. 2007
    ..Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA...
  32. ncbi request reprint Thymic generation and selection of CD25+CD4+ regulatory T cells: implications of their broad repertoire and high self-reactivity for the maintenance of immunological self-tolerance
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Novartis Found Symp 252:6-16; discussion 16-23, 106-14. 2003
    ....
  33. pmc Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation
    Yasushi Onishi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Proc Natl Acad Sci U S A 105:10113-8. 2008
    ..Both steps prevent antigen-reactive naïve T cells from being activated by antigen-presenting DCs, resulting in specific immune suppression and tolerance...
  34. doi request reprint CTLA-4 control over Foxp3+ regulatory T cell function
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Science 322:271-5. 2008
    ..Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells...
  35. ncbi request reprint The role of regulatory T cells in controlling immunologic self-tolerance
    Takeshi Takahashi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    Int Rev Cytol 225:1-32. 2003
    ..The CD25+CD4+ regulatory T cells are produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling various immune reactions...
  36. ncbi request reprint Emerging challenges in regulatory T cell function and biology
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Science 317:627-9. 2007
    ..From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses...
  37. doi request reprint Regulatory T cells exert checks and balances on self tolerance and autoimmunity
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Nat Immunol 11:7-13. 2010
    ....
  38. ncbi request reprint Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells
    Haruhiko Yagi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Int Immunol 16:1643-56. 2004
    ..Furthermore, regulatory T cells de novo produced from normal naive T cells by FOXP3 transduction can be instrumental for treatment of autoimmune/inflammatory diseases and negative control of various immune responses...
  39. doi request reprint Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansion
    Makoto Miyara
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Allergy Clin Immunol 123:749-55; quiz 756-7. 2009
    ..The feasibility of such Treg cell-based therapeutic strategies is discussed based on recent advances in our understanding of the molecular and cellular basis of Treg cell development and function...
  40. ncbi request reprint The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation
    A Yoshizawa
    Kyoto University Graduate School of Medicine, Kyoto, Japan
    Transplant Proc 37:37-9. 2005
    ..The purpose of this study was to determine whether Tregs contributed functionally to the mechanisms of graft acceptance...
  41. ncbi request reprint Regulatory T cells as potential immunotherapy in allergy
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Curr Opin Allergy Clin Immunol 6:482-8. 2006
    ..Here we discuss recent advances in the field of regulatory T cells and how this knowledge can be exploited to treat and prevent allergy...
  42. ncbi request reprint Regulatory T cells: roles of T cell receptor for their development and function
    Naganari Ohkura
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto, 606 8507, Japan
    Semin Immunopathol 32:95-106. 2010
    ....
  43. ncbi request reprint Regulatory T cells in immune surveillance and treatment of cancer
    Tomoyuki Yamaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Semin Cancer Biol 16:115-23. 2006
    ..A combination of depletion or attenuation of T(R) cells and concomitant stimulation of effector T cells, systemically or locally in tumors, may be a feasible immunotherapy for cancer...
  44. ncbi request reprint [T cell mediated immunoregulation and autoimmune disease]
    Takeshi Takahashi
    Tanpakushitsu Kakusan Koso 47:2331-5. 2002
  45. ncbi request reprint Emerging possibilities in the development and function of regulatory T cells
    Kajsa Wing
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin 53, Kawahara cho, Sakyoku, Kyoto 606 8507, Japan
    Int Immunol 18:991-1000. 2006
    ..In this review we attempt to highlight the current controversies and directions in which this exciting field is moving...
  46. ncbi request reprint Natural regulatory T cells: mechanisms of suppression
    Makoto Miyara
    Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606 8507, Japan
    Trends Mol Med 13:108-16. 2007
    ..Further studies of suppression and search for Treg-specific cell surface molecules are required for potential clinical application to treat and prevent immunological diseases and to control immune responses for the benefit of the host...
  47. ncbi request reprint Spontaneous large-scale lymphoid neogenesis and balanced autoimmunity versus tolerance in the stomach of H+/K+-ATPase-reactive TCR transgenic mouse
    Tomoya Katakai
    Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    J Immunol 177:7858-67. 2006
    ..e., the balance of self-reactivity and tolerance, in the local environment has an impact...
  48. ncbi request reprint Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor liver transplantation
    Takaaki Koshiba
    Department of Transplantation and Immunology, Horizontal Medical Research Organization, Faculty of Medicine, Kyoto University, 54 Kawaramachi Shogoin, Sakyo ku, Kyoto City 606 8507, Japan
    Transpl Immunol 17:94-7. 2007
    ..This warrants serial protocol biopsy before and after complete cessation of immunosuppression even in the presence of normal liver function...
  49. pmc CD4+ regulatory cells as a potential immunotherapy
    Zoltan Fehervari
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    Philos Trans R Soc Lond B Biol Sci 360:1647-61. 2005
    ..We will focus here on harnessing the suppressive abilities of both these families of regulatory cells and how this should give us access to a potent cell-based immunotherapy appropriate for clinical application...
  50. pmc CD4+ Tregs and immune control
    Zoltan Fehervari
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Clin Invest 114:1209-17. 2004
    ..The identification of specific molecular markers in both human and murine immune systems has enabled the unprecedented investigation of these cells and should prove key to ultimately unlocking their clinical potential...
  51. ncbi request reprint Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells
    Zoltan Fehervari
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogo in 53, Sakyo ku, Kyoto 606 8507, Japan
    Int Immunol 16:1769-80. 2004
    ..DC also blocked normal CD4+CD25+ TR cell-mediated suppression partially via IL-6 secretion. DC therefore possess novel mechanisms to control the suppressive ability, expansion and/or differentiation of CD4+CD25+ TR cells in vivo...
  52. ncbi request reprint Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease
    Takeshi Takahashi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    Curr Mol Med 3:693-706. 2003
    ..Thus, this unique population of regulatory T cells can be exploited to control pathological as well as physiological immune responses...
  53. ncbi request reprint Development and function of CD25+CD4+ regulatory T cells
    Zoltan Fehervari
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Shogo in 53, Sakyo ku, Kyoto 606 8507, Japan
    Curr Opin Immunol 16:203-8. 2004
    ....
  54. doi request reprint FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agents
    Naganari Ohkura
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Trends Pharmacol Sci 32:158-66. 2011
    ..However, it is envisaged that pharmacological control of the function and development of Tregs by targeting FOXP3 or Treg-associated molecules will enable better control of immune responses in various clinical settings...
  55. doi request reprint Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function
    Satoshi Tanaka
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Immunol 185:2295-305. 2010
    ..It also changes the dependency of disease development on environmental stimuli. These findings collectively provide a model of how genetic anomaly of T cell signaling contributes to the development of autoimmune disease...
  56. doi request reprint Differential control of allo-antigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation tolerance
    Kanji Nagahama
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    Int Immunol 21:379-91. 2009
    ....
  57. ncbi request reprint Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor liver transplantation
    Ying Li
    Department of Transplantation and Immunology, Horizontal Medical Research Organization, Transplant Tolerance Unit, Kyoto University, Faculty of Medicine, Kyoto, Japan
    Am J Transplant 4:2118-25. 2004
    ..Although the contribution of those subsets to the tolerant state remains elusive, the results may provide important clues for reliable indicators of tolerance after LDLT...
  58. ncbi request reprint Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced TNF receptor family-related protein(high), Foxp3-expressing CD25+ and CD25- regulatory T cells
    Masahiro Ono
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    J Immunol 176:4748-56. 2006
    ..GITR(high), Foxp3-expressing natural Treg represent a potential target for the treatment and prevention of these diseases...
  59. ncbi request reprint Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice
    Noriko Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Nature 426:454-60. 2003
    ..Thymic production of arthritogenic T cells due to a genetically determined selection shift of the T-cell repertoire towards high self-reactivity might also be crucial to the development of disease in a subset of patients with RA...
  60. ncbi request reprint The dichotomous role of IL-2: tolerance versus immunity
    Zoltan Fehervari
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Trends Immunol 27:109-11. 2006
    ..A recent study examining the role of IL-2 in the peripheral generation of regulatory T cells from apparently naïve T cells has gone some way to reconciling the seemingly opposing functions of this cytokine...
  61. ncbi request reprint Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1
    Masahiro Ono
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
    Nature 446:685-9. 2007
    ..This transcriptional control of T(R)-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses...
  62. doi request reprint The presence of Foxp3 expressing T cells within grafts of tolerant human liver transplant recipients
    Ying Li
    Innovation Center for Immunoregulation Technologies and Drugs, Transplant Tolerance Unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Transplantation 86:1837-43. 2008
    ..The results were compared with biopsies from the recipients on maintenance immunosuppression (Gr-IS), grafts removed because of chronic rejection (Gr-CR), or normal liver (Gr-NL)...
  63. doi request reprint Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantation
    Mami Yoshitomi
    Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Transplantation 87:606-14. 2009
    ..Operational tolerance is defined as long-term acceptance of a transplanted organ after complete cessation of immunosuppression (IS), but may not always protect against antigen-dependent changes in graft morphology...
  64. doi request reprint Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor
    Makoto Miyara
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
    Immunity 30:899-911. 2009
    ....
  65. doi request reprint Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis
    Yoshinaga Ito
    Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Arthritis Rheum 60:2294-303. 2009
    ..The involvement of IL-17-producing gamma/delta T cells in SKG mice with autoimmune arthritis and patients with rheumatoid arthritis (RA) was also investigated...
  66. doi request reprint Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanoma
    H Fujii
    Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Kawahara cho, Shogoin, Sakyo Kyoto 606 8507, Japan
    Br J Dermatol 164:1052-60. 2011
    ..However, this idea is challenged by recent evidence that the 'FOXP3+ Treg' fraction in fact contains activated 'nonregulatory' T cells. Also, FOXP3+ T cells are reported to have functionally and kinetically distinct subsets...
  67. ncbi request reprint Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis
    Naoshi Sugimoto
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Int Immunol 18:1197-209. 2006
    ..Some of these genes are controlled by Foxp3, and others are not. These genes, in particular, Gpr83, Ecm1 and Helios, could potentially be used as specific markers for natural Treg...
  68. ncbi request reprint [Peripheral tolerance to allergen mediated by regulatory T cells]
    Tomoyuki Yamaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
    Nihon Rinsho 67:2063-70. 2009
    ..Immune reactions in tumor immunity and autoimmune diseases can be monitored and controlled in a novel strategy by targeting Tregs...
  69. ncbi request reprint Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor
    Tomoyuki Yamaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    Immunity 27:145-59. 2007
    ..Thus, specific manipulation of FR4(hi)CD25(+)CD4(+) Treg cells helps control ongoing immune responses...
  70. pmc Complement drives Th17 cell differentiation and triggers autoimmune arthritis
    Motomu Hashimoto
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 207:1135-43. 2010
    ..Blockade of C5aR may thus be beneficial for controlling Th17-mediated inflammation and autoimmune disease...
  71. ncbi request reprint [Etiology of rheumatoid arthritis in an animal model]
    Shimon Sakaguchi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
    Nihon Rinsho 60:2259-61. 2002
  72. ncbi request reprint A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model
    Hyun Jeong Ko
    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
    Cancer Res 67:7477-86. 2007
    ..When combined with immunotherapies, gemcitabine offers a promising strategy for the Ag-specific treatment of human cancer...
  73. ncbi request reprint IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells
    Xingmin Zhang
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Int Immunol 16:249-56. 2004
    ....
  74. ncbi request reprint Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells
    Fumiko Kanamaru
    Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    J Immunol 172:7306-14. 2004
    ..Our results highlight evidence that GITR acts as a potent and unique costimulator for an early CD4+ T cell activation...
  75. ncbi request reprint Foxp3: a critical regulator of the development and function of regulatory T cells
    Shohei Hori
    Research Unit for Immune Homeostasis, RIKEN Research Center for Allergy and Immunology, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Microbes Infect 6:745-51. 2004
    ..This review discusses the critical role for this transcription factor in the development and function of regulatory T cells...
  76. ncbi request reprint CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene
    Yasushi Takahata
    Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi ku, Fukuoka, Japan
    Exp Hematol 32:622-9. 2004
    ..To address the role of cord blood (CB) CD25+CD4+ T cells, the gene expressions and function of this subset were analyzed...
  77. ncbi request reprint 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...
  78. pmc GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host disease
    Stephanie J Muriglan
    Department of Medicine and Immunology, Memorial Sloan Kettering Cancer Center, Kettering 425, Mailbox 111, 1275 York Ave, New York, NY 10021, USA
    J Exp Med 200:149-57. 2004
    ..Our findings indicate that GITR has opposite effects on the regulation of alloreactive CD4(+) and CD8(+) T cells...
  79. ncbi request reprint 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
    ....
  80. ncbi request reprint Conversion of alloantigen-specific CD8+ T cell anergy to CD8+ T cell priming through in vivo ligation of glucocorticoid-induced TNF receptor
    Juyang Kim
    Immunomodulation Research Center IRC and Department of Biological Science, University of Ulsan, San29, Mukeo Dong, Nam Ku, Ulsan, Republic of Korea
    J Immunol 176:5223-31. 2006
    ..In sum, our data suggest GITR as an important costimulatory molecule regulating cGVHD vs aGVHD and as a target for therapeutic intervention in a variety of related diseases...
  81. ncbi request reprint CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice
    Tomohisa Nishioka
    Section of Immunology, Department of Mechanism of Aging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan
    J Immunol 176:6586-93. 2006
    ..These results suggest that the age-related decline in T cell-mediated immune responses is ascribable to changes in the CD4+CD25- T cell population and not to a functional augmentation of suppressive CD4+CD25+ T cells...
  82. ncbi request reprint Analysis of the underlying cellular mechanisms of anti-CD154-induced graft tolerance: the interplay of clonal anergy and immune regulation
    Sergio A Quezada
    Department of Microbiology and Immunology, Dartmouth Medical School, and Norris Cotton Cancer Center, Medical Center Drive, Lebanon, NH 03756, USA
    J Immunol 175:771-9. 2005
    ..Finally, it is shown that the suppression is long-lived, and in the absence of anti-CD154 and donor-specific transfusion, these T(reg) can chronically suppress effector cell responses, allowing long-lived graft acceptance...
  83. ncbi request reprint Regulatory T cells, derived from naïve CD4+CD25- T cells by in vitro Foxp3 gene transfer, can induce transplantation tolerance
    Jian Guo Chai
    Transplantation Biology Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London
    Transplantation 79:1310-6. 2005
    ..This study investigated whether Treg cells generated from naive CD4+ T cells by Foxp3 gene transfer could induce transplantation tolerance...
  84. ncbi request reprint [Liver transplantation]
    Eiji Nishimura
    Department of Transplantation and Immunology, Faculty of Medicine, Kyoto University
    Nihon Rinsho 63:670-7. 2005
  85. ncbi request reprint Glucocorticoid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunity
    Teresa Ramirez-Montagut
    Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Immunol 176:6434-42. 2006
    ..Thus, we conclude that overall, GITR stimulation overcomes self-tolerance/ignorance and enhances T cell-mediated antitumor activity with minimal autoimmunity...
  86. pmc Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells
    Hiroyoshi Nishikawa
    Second Department of Internal Medicine, Mie University School of Medicine, Mie 514 8507, Japan
    J Exp Med 201:681-6. 2005
    ..We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4(+) CD25(+) T reg cells...
  87. ncbi request reprint NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner
    Fumiko Kajiura
    Department of Molecular and Environmental Pathology, School of Medicine, University of Tokushima, Tokushima, Japan
    J Immunol 172:2067-75. 2004
    ....
  88. ncbi request reprint Peacekeepers of the immune system
    Zoltan Fehervari
    Department of Pathology, University of Cambridge
    Sci Am 295:56-63. 2006
  89. ncbi request reprint 4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells
    Beom K Choi
    Immunomodulation Research Center, University of Ulsan, Korea
    J Leukoc Biol 75:785-91. 2004
    ..It is interesting that anti-4-1BB-mediated but not anti-GITR-directed inhibition was more potent when Tr cells were preactivated. Collectively, these data indicate that 4-1BB signaling is critical in Tr cell immunity...
  90. pmc Glucocorticoid-induced tumour necrosis factor receptor family-related receptor signalling exacerbates hapten-induced colitis by CD4+ T cells
    Sun K Lee
    The Immunomodulation Research Center, University of Ulsan, Ulsan, Korea
    Immunology 119:479-87. 2006
    ..Taken together, this study demonstrated that GITR signalling on CD4(+) T cells is involved in the development and progress of colitis by enhancing both T helper type 1 (Th1) and Th2 type responses...
  91. ncbi request reprint Control of autoimmunity by naturally arising regulatory CD4+ T cells
    Shohei Hori
    Laboratory of Immunopathology, Research Center for Allergy and Immunology, The Institute for Physical and Chemical Research RIKEN, Yokohama 230 0045, Japan
    Adv Immunol 81:331-71. 2003
    ..Furthermore, reduction or dysfunction of the CD25+ CD4+ regulatory T cell population can be responsible for certain autoimmune diseases in humans...
  92. ncbi request reprint Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice
    Noriyuki Kuroda
    Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan
    J Immunol 174:1862-70. 2005
    ..With the use of inbred Aire-deficient mouse strains, we also demonstrate the presence of some additional factor(s) that determine the target-organ specificity of the autoimmune disease caused by Aire deficiency...
  93. ncbi request reprint Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism
    David C Gondek
    Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03756, USA
    J Immunol 174:1783-6. 2005
    ..In summary, GZ-B is one of the key mechanisms through which CD4+CD25+ Treg induce cell contact-mediated suppression...
  94. ncbi request reprint 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...
  95. ncbi request reprint Regulatory cells in transplantation
    Kathryn J Wood
    Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
    Novartis Found Symp 252:177-88; discussion 188-93, 203-10. 2003
    ....