Research Topics
Species | S SakaguchiSummaryAffiliation: Kyoto University Country: Japan Publications
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Publications
Animal models of arthritis caused by systemic alteration of the immune systemShimon 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...
Chronic arthritis leads to disturbances in the bone collagen networkJoana 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...
Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1Shimon 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...
Dynamics of peripheral tolerance and immune regulation mediated by TregShimon 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...
Regulatory T cells and immune toleranceShimon 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...
Regulatory T cells in the past and for the futureShimon Sakaguchi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
Eur J Immunol 38:901-37. 2008
Regulatory T cells - a brief history and perspectiveShimon 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...
Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune diseaseS 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...
Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-selfShimon 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...
Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune diseaseShimon Sakaguchi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Immunol Rev 212:8-27. 2006....
Regulatory T cellsShimon 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
Regulatory T cells in immunologic self-tolerance and autoimmune diseaseShimon 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...
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...
Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responsesShimon Sakaguchi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
Annu Rev Immunol 22:531-62. 2004....
Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptorsShimon Sakaguchi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
J Exp Med 197:397-401. 2003
The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or peripheryShimon 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...
FOXP3+ regulatory T cells in the human immune systemShimon 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...
Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation toleranceS 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...
Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunityS 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...
Animal models of autoimmunity and their relevance to human diseasesS 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...
Immunologic tolerance maintained by regulatory T cells: implications for autoimmunity, tumor immunity and transplantation toleranceShimon Sakaguchi
Dep. Exp. Pathol, Inst. Frontier Med. Sci, Kyoto Univ, Kyoto, Japan
Vox Sang 83:151-3. 2002
Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4T 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...
Naturally arising CD25+CD4+ regulatory T cells in tumor immunityT 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...
[Regulatory T cells]Takatoku Oida
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
Nippon Rinsho 63:154-8. 2005
Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in miceHiroshi 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...
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-toleranceShimon 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....
T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritisKeiji 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...
Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cellsEiji Nishimura
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Faculty of Medicine, Kyoto University, Japan
Int Immunol 16:1189-201. 2004....
CTLA-4 control over Foxp3+ regulatory T cell functionKajsa 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...
Emerging challenges in regulatory T cell function and biologyShimon 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...
Regulatory T cells exert checks and balances on self tolerance and autoimmunityKajsa Wing
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Nat Immunol 11:7-13. 2010....
Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturationYasushi 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...
The role of regulatory T cells in controlling immunologic self-toleranceTakeshi 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...
A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible miceHiroyuki Yoshitomi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
J Exp Med 201:949-60. 2005....
Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralizationRuka 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...
The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantationA Yoshizawa
Kyoto University Graduate School of Medicine, Kyoto, Japan
Transplant Proc 37:37-9. 2005..DISCUSSION: These findings suggest that donor alloantigen specific regulation by Tregs is one of multiple mechanisms that may contribute to the maintenance of liver graft survival in the absence of immunosuppression...
Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansionMakoto 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...
Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cellsHaruhiko 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...
CD4+ regulatory cells as a potential immunotherapyZoltan 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...
Emerging possibilities in the development and function of regulatory T cellsKajsa 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...
[T cell mediated immunoregulation and autoimmune disease]Takeshi Takahashi
Tanpakushitsu Kakusan Koso 47:2331-5. 2002
Regulatory T cells in immune surveillance and treatment of cancerTomoyuki 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...
Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune diseaseTakeshi 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...
Clinical, immunological, and pathological aspects of operational tolerance after pediatric living-donor liver transplantationTakaaki 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...
Regulatory T cells: roles of T cell receptor for their development and functionNaganari 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....
Regulatory T cells as potential immunotherapy in allergyKajsa 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...
Spontaneous large-scale lymphoid neogenesis and balanced autoimmunity versus tolerance in the stomach of H+/K+-ATPase-reactive TCR transgenic mouseTomoya 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...
Development and function of CD25+CD4+ regulatory T cellsZoltan 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....
CD4+ Tregs and immune controlZoltan 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...
Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cellsZoltan 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...
Natural regulatory T cells: mechanisms of suppressionMakoto 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...
FOXP3+ regulatory T cells: control of FOXP3 expression by pharmacological agentsNaganari 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...
Differential control of allo-antigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation toleranceKanji Nagahama
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
Int Immunol 21:379-91. 2009....
Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor liver transplantationYing 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...
Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced TNF receptor family-related protein(high), Foxp3-expressing CD25+ and CD25- regulatory T cellsMasahiro 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...
Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cellsKuibeom 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...
Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in miceNoriko 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...
Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell functionSatoshi 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...
Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritisYoshinaga 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...
Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantationMami 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...
The presence of Foxp3 expressing T cells within grafts of tolerant human liver transplant recipientsYing 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)...
Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal modelKeiji 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...
Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1Masahiro 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...
Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factorMakoto Miyara
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Immunity 30:899-911. 2009....
The dichotomous role of IL-2: tolerance versus immunityZoltan 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...
Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanomaH 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...
Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysisNaoshi 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...
[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...
Complement drives Th17 cell differentiation and triggers autoimmune arthritisMotomu 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...
Control of immune responses by antigen-specific regulatory T cells expressing the folate receptorTomoyuki 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...
[Etiology of rheumatoid arthritis in an animal model]Shimon Sakaguchi
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
Nippon Rinsho 60:2259-61. 2002
Control of regulatory T cell development by the transcription factor Foxp3Shohei 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...
Glucocorticoid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunityTeresa 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...
Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-toleranceJun 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...
Regulatory cells in transplantationKathryn 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....
CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged miceTomohisa 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...
Conversion of alloantigen-specific CD8+ T cell anergy to CD8+ T cell priming through in vivo ligation of glucocorticoid-induced TNF receptorJuyang 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...
Analysis of the underlying cellular mechanisms of anti-CD154-induced graft tolerance: the interplay of clonal anergy and immune regulationSergio 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...
4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cellsBeom 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...
Regulatory T cells in transplantation toleranceKathryn J Wood
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
Nat Rev Immunol 3:199-210. 2003....
Regulatory T cells, derived from naïve CD4+CD25- T cells by in vitro Foxp3 gene transfer, can induce transplantation toleranceJian 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...
Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanismDavid 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...
Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient miceNoriyuki 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...
GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host diseaseStephanie 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...
Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cellsHiroyoshi 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...
A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor modelHyun 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...
CD25+CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) geneYasushi 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...
Foxp3: a critical regulator of the development and function of regulatory T cellsShohei 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...
Peacekeepers of the immune systemZoltan Fehervari
Department of Pathology, University of Cambridge
Sci Am 295:56-63. 2006
Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cellsFumiko 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...
NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent mannerFumiko Kajiura
Department of Molecular and Environmental Pathology, School of Medicine, University of Tokushima, Tokushima, Japan
J Immunol 172:2067-75. 2004....
IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cellsXingmin Zhang
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Int Immunol 16:249-56. 2004....
Control of autoimmunity by naturally arising regulatory CD4+ T cellsShohei 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...
[Liver transplantation]Eiji Nishimura
Department of Transplantation and Immunology, Faculty of Medicine, Kyoto University
Nippon Rinsho 63:670-7. 2005
Glucocorticoid-induced tumour necrosis factor receptor family-related receptor signalling exacerbates hapten-induced colitis by CD4+ T cellsSun 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...
