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*
Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; and
Department of Dermatology, University of Tsukuba, School of Medicine, Tsukuba, Japan
This study shows that the normal thymus produces immunoregulatory
CD25+4+8- thymocytes capable of
controlling self-reactive T cells. Transfer of thymocyte suspensions
depleted of CD25+4+8- thymocytes,
which constitute 
5% of steroid-resistant mature
CD4+8- thymocytes in normal naive mice,
produces various autoimmune diseases in syngeneic athymic nude mice.
These CD25+4+8- thymocytes are
nonproliferative (anergic) to TCR stimulation in vitro, but potently
suppress the proliferation of other CD4+8- or
CD4-8+ thymocytes; breakage of their anergic
state in vitro by high doses of IL-2 or anti-CD28 Ab simultaneously
abrogates their suppressive activity; and transfer of such
suppression-abrogated thymocyte suspensions produces autoimmune disease
in nude mice. These immunoregulatory
CD25+4+8- thymocytes/T cells are
functionally distinct from activated CD25+4+ T
cells derived from CD25-4+ thymocytes/T cells
in that the latter scarcely exhibits suppressive activity in vitro,
although both CD25+4+ populations express a
similar profile of cell surface markers. Furthermore, the
CD25+4+8- thymocytes appear to
acquire their anergic and suppressive property through the thymic
selection process, since TCR transgenic mice develop similar
anergic/suppressive CD25+4+8-
thymocytes and CD25+4+ T cells that
predominantly express TCRs utilizing endogenous 
-chains, but
RAG-2-deficient TCR transgenic mice do not. These results taken
together indicate that anergic/suppressive
CD25+4+8- thymocytes and
peripheral T cells in normal naive mice may constitute a common T cell
lineage functionally and developmentally distinct from other T cells,
and that production of this unique immunoregulatory T cell population
can be another key function of the thymus in maintaining immunologic
self-tolerance.
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D. T. Nardelli, T. F. Warner, S. M. Callister, and R. F. Schell Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged with Borrelia spp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production. Clin. Vaccine Immunol., August 1, 2006; 13(8): 884 - 891. [Abstract] [Full Text] [PDF]
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K. J. Scalapino, Q. Tang, J. A. Bluestone, M. L. Bonyhadi, and D. I. Daikh Suppression of Disease in New Zealand Black/New Zealand White Lupus-Prone Mice by Adoptive Transfer of Ex Vivo Expanded Regulatory T Cells J. Immunol., August 1, 2006; 177(3): 1451 - 1459. [Abstract] [Full Text] [PDF]
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H. W. Lim, H. E. Broxmeyer, and C. H. Kim Regulation of Trafficking Receptor Expression in Human Forkhead Box P3+ Regulatory T Cells J. Immunol., July 15, 2006; 177(2): 840 - 851. [Abstract] [Full Text] [PDF]
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D. Valmori, V. Tosello, N. E. Souleimanian, E. Godefroy, L. Scotto, Y. Wang, and M. Ayyoub Rapamycin-Mediated Enrichment of T Cells with Regulatory Activity in Stimulated CD4+ T Cell Cultures Is Not Due to the Selective Expansion of Naturally Occurring Regulatory T Cells but to the Induction of Regulatory Functions in Conventional CD4+ T Cells J. Immunol., July 15, 2006; 177(2): 944 - 949. [Abstract] [Full Text] [PDF]
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P. Lan, N. Tonomura, A. Shimizu, S. Wang, and Y.-G. Yang Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation Blood, July 15, 2006; 108(2): 487 - 492. [Abstract] [Full Text] [PDF]
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J. Y.-S. Tsang, N. O. S. Camara, E. Eren, H. Schneider, C. Rudd, G. Lombardi, and R. Lechler Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells J. Leukoc. Biol., July 1, 2006; 80(1): 145 - 151. [Abstract] [Full Text] [PDF]
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 P. Alard, J. N. Manirarora, S. A. Parnell, J. L. Hudkins, S. L. Clark, and M. M. Kosiewicz Deficiency in NOD Antigen-Presenting Cell Function May Be Responsible for Suboptimal CD4+CD25+ T-Cell-Mediated Regulation and Type 1 Diabetes Development in NOD Mice. Diabetes, July 1, 2006; 55(7): 2098 - 2105. [Abstract] [Full Text] [PDF]
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K. Wing, Z. Fehervari, and S. Sakaguchi Emerging possibilities in the development and function of regulatory T cells Int. Immunol., July 1, 2006; 18(7): 991 - 1000. [Abstract] [Full Text] [PDF]
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M. Shimoda, F. Mmanywa, S. K. Joshi, T. Li, K. Miyake, J. Pihkala, J. A. Abbas, and P. A. Koni Conditional Ablation of MHC-II Suggests an Indirect Role for MHC-II in Regulatory CD4 T Cell Maintenance. J. Immunol., June 1, 2006; 176(11): 6503 - 6511. [Abstract] [Full Text] [PDF]
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T. Nishioka, J. Shimizu, R. Iida, S. Yamazaki, and S. Sakaguchi CD4+CD25+Foxp3+ T Cells and CD4+CD25-Foxp3+ T Cells in Aged Mice. J. Immunol., June 1, 2006; 176(11): 6586 - 6593. [Abstract] [Full Text] [PDF]
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T. L. Vanasek, S. L. Nandiwada, M. K. Jenkins, and D. L. Mueller CD25+Foxp3+ Regulatory T Cells Facilitate CD4+ T Cell Clonal Anergy Induction during the Recovery from Lymphopenia J. Immunol., May 15, 2006; 176(10): 5880 - 5889. [Abstract] [Full Text] [PDF]
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 M C Fantini, C Becker, I Tubbe, A Nikolaev, H A Lehr, P Galle, and M F Neurath Transforming growth factor {beta} induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis Gut, May 1, 2006; 55(5): 671 - 680. [Abstract] [Full Text] [PDF]
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K. S. Nicolson, E. J. O'Neill, A. Sundstedt, H. B. Streeter, S. Minaee, and D. C. Wraith Antigen-Induced IL-10+ Regulatory T Cells Are Independent of CD25+ Regulatory Cells for Their Growth, Differentiation, and Function J. Immunol., May 1, 2006; 176(9): 5329 - 5337. [Abstract] [Full Text] [PDF]
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Z.-Z. Yang, A. J. Novak, M. J. Stenson, T. E. Witzig, and S. M. Ansell Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma Blood, May 1, 2006; 107(9): 3639 - 3646. [Abstract] [Full Text] [PDF]
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M. A. Gavin, T. R. Torgerson, E. Houston, P. deRoos, W. Y. Ho, A. Stray-Pedersen, E. L. Ocheltree, P. D. Greenberg, H. D. Ochs, and A. Y. Rudensky Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development PNAS, April 25, 2006; 103(17): 6659 - 6664. [Abstract] [Full Text] [PDF]
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M. Ono, J. Shimizu, Y. Miyachi, and S. Sakaguchi Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Proteinhigh, Foxp3-Expressing CD25+ and CD25- Regulatory T Cells. J. Immunol., April 15, 2006; 176(8): 4748 - 4756. [Abstract] [Full Text] [PDF]
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 H. Keino, M. Takeuchi, T. Kezuka, T. Hattori, M. Usui, O. Taguchi, J. W. Streilein, and J. Stein-Streilein Induction of Eye-Derived Tolerance Does Not Depend on Naturally Occurring CD4+CD25+ T Regulatory Cells. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1047 - 1055. [Abstract] [Full Text] [PDF]
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S. Koonpaew, S. Shen, L. Flowers, and W. Zhang LAT-mediated signaling in CD4+CD25+ regulatory T cell development J. Exp. Med., January 23, 2006; 203(1): 119 - 129. [Abstract] [Full Text] [PDF]
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A. Sanchez-Fueyo, S. Sandner, A. Habicht, C. Mariat, J. Kenny, N. Degauque, X. X. Zheng, T. B. Strom, L. A. Turka, and M. H. Sayegh Specificity of CD4+CD25+ Regulatory T Cell Function in Alloimmunity J. Immunol., January 1, 2006; 176(1): 329 - 334. [Abstract] [Full Text] [PDF]
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A. T. Endharti, M. Rifa' I, Z. Shi, Y. Fukuoka, Y. Nakahara, Y. Kawamoto, K. Takeda, K.-i. Isobe, and H. Suzuki Cutting Edge: CD8+CD122+ Regulatory T Cells Produce IL-10 to Suppress IFN-{gamma} Production and Proliferation of CD8+ T Cells J. Immunol., December 1, 2005; 175(11): 7093 - 7097. [Abstract] [Full Text] [PDF]
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R. J. DiPaolo, D. D. Glass, K. E. Bijwaard, and E. M. Shevach CD4+CD25+ T Cells Prevent the Development of Organ-Specific Autoimmune Disease by Inhibiting the Differentiation of Autoreactive Effector T Cells J. Immunol., December 1, 2005; 175(11): 7135 - 7142. [Abstract] [Full Text] [PDF]
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 D. Wolf, A. M. Wolf, H. Rumpold, H. Fiegl, A. G. Zeimet, E. Muller-Holzner, M. Deibl, G. Gastl, E. Gunsilius, and C. Marth The Expression of the Regulatory T Cell-Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer Clin. Cancer Res., December 1, 2005; 11(23): 8326 - 8331. [Abstract] [Full Text] [PDF]
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I. Durinovic-Bello, E. Jelinek, M. Schlosser, T. Eiermann, B. O. Boehm, W. Karges, L. Marchand, and C. Polychronakos Class III Alleles at the Insulin VNTR Polymorphism Are Associated With Regulatory T-Cell Responses to Proinsulin Epitopes in HLA-DR4, DQ8 Individuals Diabetes, December 1, 2005; 54(suppl_2): S18 - S24. [Abstract] [Full Text] [PDF]
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P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk Molecular Signature of Recent Thymic Selection Events on Effector and Regulatory CD4+ T Lymphocytes J. Immunol., November 1, 2005; 175(9): 5751 - 5758. [Abstract] [Full Text] [PDF]
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A. Skapenko, J. R. Kalden, P. E. Lipsky, and H. Schulze-Koops The IL-4 Receptor {alpha}-Chain-Binding Cytokines, IL-4 and IL-13, Induce Forkhead Box P3-Expressing CD25+CD4+ Regulatory T Cells from CD25-CD4+ Precursors J. Immunol., November 1, 2005; 175(9): 6107 - 6116. [Abstract] [Full Text] [PDF]
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K. Siegmund, M. Feuerer, C. Siewert, S. Ghani, U. Haubold, A. Dankof, V. Krenn, M. P. Schon, A. Scheffold, J. B. Lowe, et al. Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo Blood, November 1, 2005; 106(9): 3097 - 3104. [Abstract] [Full Text] [PDF]
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J. D. Fontenot, J. L. Dooley, A. G. Farr, and A. Y. Rudensky Developmental regulation of Foxp3 expression during ontogeny J. Exp. Med., October 3, 2005; 202(7): 901 - 906. [Abstract] [Full Text] [PDF]
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B. Bienvenu, B. Martin, C. Auffray, C. Cordier, C. Becourt, and B. Lucas Peripheral CD8+CD25+ T Lymphocytes from MHC Class II-Deficient Mice Exhibit Regulatory Activity J. Immunol., July 1, 2005; 175(1): 246 - 253. [Abstract] [Full Text] [PDF]
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C. R. Ruprecht, M. Gattorno, F. Ferlito, A. Gregorio, A. Martini, A. Lanzavecchia, and F. Sallusto Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia J. Exp. Med., June 6, 2005; 201(11): 1793 - 1803. [Abstract] [Full Text] [PDF]
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