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Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Thymectomy of susceptible strains of mice on day 3 of life results in a spectrum of organ-specific autoimmunity that can be prevented by reconstitution of the thymectomized animals early in life with normal adult lymphocytes. The effectors and suppressors of autoimmunity in this model have been convincingly shown to be CD4+ T cells. It has been demonstrated recently that the regulatory CD4+ T cells that prevent disease coexpress CD25. We have further characterized the population of CD4+CD25+ immunoregulatory cells and demonstrated that they can suppress not only the induction of disease post-thymectomy, but can also efficiently suppress disease induced by cloned autoantigen-specific effector cells. Furthermore, the CD4+CD25+ T cells appear to be members of a unique lineage of regulatory T cells, as the induction of CD25 expression on a monospecific population of T cells derived from TCR transgenic SCID mice did not result in suppression of post-thymectomy autoimmunity. In addition, the TCR transgenic SCID mice were highly susceptible to autoimmune disease induced by the cloned line of autoantigen-specific effectors, while normal mice were relatively resistant. The capacity of the cloned line to transfer disease to nu/nu recipients could be inhibited by normal spleen cell populations containing CD4+CD25+ cells and by purified CD4+CD25+ cells. Although the target Ag(s) and mechanism of action of the CD4+CD25+ T cells remain to be determined, it is likely that they also play an important role in modulating other autoimmune diseases that are mediated by activation of "ignorant" self-reactive T cells present in the normal peripheral lymphocyte pool.
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I. W. Nasr, Y. Wang, G. Gao, S. Deng, L. Diggs, D. M. Rothstein, G. Tellides, F. G. Lakkis, and Z. Dai Testicular Immune Privilege Promotes Transplantation Tolerance by Altering the Balance between Memory and Regulatory T Cells J. Immunol., May 15, 2005; 174(10): 6161 - 6168. [Abstract] [Full Text] [PDF]
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S. You, M. Belghith, S. Cobbold, M.-A. Alyanakian, C. Gouarin, S. Barriot, C. Garcia, H. Waldmann, J.-F. Bach, and L. Chatenoud Autoimmune Diabetes Onset Results From Qualitative Rather Than Quantitative Age-Dependent Changes in Pathogenic T-Cells Diabetes, May 1, 2005; 54(5): 1415 - 1422. [Abstract] [Full Text] [PDF]
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 D. Wolf, K. Hochegger, A. M. Wolf, H. F. Rumpold, G. Gastl, H. Tilg, G. Mayer, E. Gunsilius, and A. R. Rosenkranz CD4+CD25+ Regulatory T Cells Inhibit Experimental Anti-Glomerular Basement Membrane Glomerulonephritis in Mice J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1360 - 1370. [Abstract] [Full Text] [PDF]
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A. P. Kohm, J. S. Williams, A. L. Bickford, J. S. McMahon, L. Chatenoud, J.-F. Bach, J. A. Bluestone, and S. D. Miller Treatment with Nonmitogenic Anti-CD3 Monoclonal Antibody Induces CD4+ T Cell Unresponsiveness and Functional Reversal of Established Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2005; 174(8): 4525 - 4534. [Abstract] [Full Text] [PDF]
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D. Lundsgaard, T. L. Holm, L. Hornum, and H. Markholst In Vivo Control of Diabetogenic T-Cells by Regulatory CD4+CD25+ T-Cells Expressing Foxp3 Diabetes, April 1, 2005; 54(4): 1040 - 1047. [Abstract] [Full Text] [PDF]
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H. Kataoka, S. Takahashi, K. Takase, S. Yamasaki, T. Yokosuka, T. Koike, and T. Saito CD25+CD4+ regulatory T cells exert in vitro suppressive activity independent of CTLA-4 Int. Immunol., April 1, 2005; 17(4): 421 - 427. [Abstract] [Full Text] [PDF]
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D. W. Smith and C. Nagler-Anderson Preventing Intolerance: The Induction of Nonresponsiveness to Dietary and Microbial Antigens in the Intestinal Mucosa J. Immunol., April 1, 2005; 174(7): 3851 - 3857. [Abstract] [Full Text] [PDF]
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P. A. Antony, C. A. Piccirillo, A. Akpinarli, S. E. Finkelstein, P. J. Speiss, D. R. Surman, D. C. Palmer, C.-C. Chan, C. A. Klebanoff, W. W. Overwijk, et al. CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells J. Immunol., March 1, 2005; 174(5): 2591 - 2601. [Abstract] [Full Text] [PDF]
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T. Alvaro, M. Lejeune, M. T. Salvado, R. Bosch, J. F. Garcia, J. Jaen, A. H. Banham, G. Roncador, C. Montalban, and M. A. Piris Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells Clin. Cancer Res., February 15, 2005; 11(4): 1467 - 1473. [Abstract] [Full Text] [PDF]
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 C Veltkamp, R B Sartor, T Giese, F Autschbach, I Kaden, R Veltkamp, D Rost, B Kallinowski, and W Stremmel Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TG{varepsilon}26 mice leading to the prevention of colitis Gut, February 1, 2005; 54(2): 207 - 214. [Abstract] [Full Text] [PDF]
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P. E. Rao, A. L. Petrone, and P. D. Ponath Differentiation and Expansion of T Cells with Regulatory Function from Human Peripheral Lymphocytes by Stimulation in the Presence of TGF-{beta} J. Immunol., February 1, 2005; 174(3): 1446 - 1455. [Abstract] [Full Text] [PDF]
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M.-L. Chen, M. J. Pittet, L. Gorelik, R. A. Flavell, R. Weissleder, H. von Boehmer, and K. Khazaie Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-{beta} signals in vivo PNAS, January 11, 2005; 102(2): 419 - 424. [Abstract] [Full Text] [PDF]
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N. Taylor, K. McConnachie, C. Calder, R. Dawson, A. Dick, J. D. Sedgwick, and J. Liversidge Enhanced Tolerance to Autoimmune Uveitis in CD200-Deficient Mice Correlates with a Pronounced Th2 Switch in Response to Antigen Challenge J. Immunol., January 1, 2005; 174(1): 143 - 154. [Abstract] [Full Text] [PDF]
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H. Sugiyama, R. Gyulai, E. Toichi, E. Garaczi, S. Shimada, S. R. Stevens, T. S. McCormick, and K. D. Cooper Dysfunctional Blood and Target Tissue CD4+CD25high Regulatory T Cells in Psoriasis: Mechanism Underlying Unrestrained Pathogenic Effector T Cell Proliferation J. Immunol., January 1, 2005; 174(1): 164 - 173. [Abstract] [Full Text] [PDF]
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 F. N. Toka, S. Suvas, and B. T. Rouse CD4+ CD25+ T Cells Regulate Vaccine-Generated Primary and Memory CD8+ T-Cell Responses against Herpes Simplex Virus Type 1 J. Virol., December 1, 2004; 78(23): 13082 - 13089. [Abstract] [Full Text] [PDF]
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D. T. Nardelli, M. A. Burchill, D. M. England, J. Torrealba, S. M. Callister, and R. F. Schell Association of CD4+ CD25+ T Cells with Prevention of Severe Destructive Arthritis in Borrelia burgdorferi-Vaccinated and Challenged Gamma Interferon-Deficient Mice Treated with Anti-Interleukin-17 Antibody Clin. Vaccine Immunol., November 1, 2004; 11(6): 1075 - 1084. [Abstract] [Full Text] [PDF]
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M. A. Salam, K. Matin, N. Matsumoto, Y. Tsuha, N. Hanada, and H. Senpuku E2f1 Mutation Induces Early Onset of Diabetes and Sjogren's Syndrome in Nonobese Diabetic Mice J. Immunol., October 15, 2004; 173(8): 4908 - 4918. [Abstract] [Full Text] [PDF]
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H. C. Dujardin, O. Burlen-Defranoux, L. Boucontet, P. Vieira, A. Cumano, and A. Bandeira Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells PNAS, October 5, 2004; 101(40): 14473 - 14478. [Abstract] [Full Text] [PDF]
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J. Kipnis, H. Avidan, R. R. Caspi, and M. Schwartz Dual effect of CD4+CD25+ regulatory T cells in neurodegeneration: A dialogue with microglia PNAS, October 5, 2004; 101(suppl_2): 14663 - 14669. [Abstract] [Full Text] [PDF]
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Y. Miura, C. J. Thoburn, E. C. Bright, M. L. Phelps, T. Shin, E. C. Matsui, W. H. Matsui, S. Arai, E. J. Fuchs, G. B. Vogelsang, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease Blood, October 1, 2004; 104(7): 2187 - 2193. [Abstract] [Full Text] [PDF]
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N. Sarween, A. Chodos, C. Raykundalia, M. Khan, A. K. Abbas, and L. S. K. Walker CD4+CD25+ Cells Controlling a Pathogenic CD4 Response Inhibit Cytokine Differentiation, CXCR-3 Expression, and Tissue Invasion J. Immunol., September 1, 2004; 173(5): 2942 - 2951. [Abstract] [Full Text] [PDF]
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B. E. Anderson, J. M. McNiff, C. Matte, I. Athanasiadis, W. D. Shlomchik, and M. J. Shlomchik Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease Blood, September 1, 2004; 104(5): 1565 - 1573. [Abstract] [Full Text] [PDF]
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B. T. Rouse and S. Suvas Regulatory Cells and Infectious Agents: Detentes Cordiale and Contraire J. Immunol., August 15, 2004; 173(4): 2211 - 2215. [Abstract] [Full Text] [PDF]
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A. L. Kinter, M. Hennessey, A. Bell, S. Kern, Y. Lin, M. Daucher, M. Planta, M. McGlaughlin, R. Jackson, S. F. Ziegler, et al. CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status J. Exp. Med., August 2, 2004; 200(3): 331 - 343. [Abstract] [Full Text] [PDF]
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C. Baecher-Allan and D. A. Hafler Suppressor T Cells in Human Diseases J. Exp. Med., August 2, 2004; 200(3): 273 - 276. [Abstract] [Full Text] [PDF]
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 K. Eriksson, L. Bellner, S. Gorander, G.-B. Lowhagen, P. Tunback, K. Rydberg, and J.-A. Liljeqvist CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals J. Gen. Virol., August 1, 2004; 85(8): 2139 - 2147. [Abstract] [Full Text] [PDF]
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E. Nishimura, T. Sakihama, R. Setoguchi, K. Tanaka, and S. Sakaguchi Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells Int. Immunol., August 1, 2004; 16(8): 1189 - 1201. [Abstract] [Full Text] [PDF]
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