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and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers1
* Lymphocyte Population Biology, Unité de Recherche Associée Centre National de la Recherche Scientifique 1961, Institut Pasteur, and
Institut National de la Santé et de la Recherche Médicale Unité 345, Centre Hospitalo-Universitaire Necker, Paris, France
We show that the lymphoid hyperplasia observed in IL-2R
- and
IL-2-deficient mice is due to the lack of a population of regulatory
cells essential for CD4 T cell homeostasis. In chimeras reconstituted
with bone marrow cells from IL-2R-deficient donors,
restitution of a population of CD25+CD4+ T
cells prevents the chaotic accumulation of lymphoid cells, and rescues
the mice from autoimmune disease and death. The reintroduction of
IL-2-producing cells in IL-2-deficient chimeras establishes a
population of CD25+CD4+ T cells, and restores
the peripheral lymphoid compartments to normal. The
CD25+CD4+ T cells regulated selectively the
number of naive CD4+ T cells transferred into T
cell-deficient hosts. The CD25+CD4+/naive CD4 T
cell ratio and the sequence of cell transfer determines the homeostatic
plateau of CD4+ T cells. Overall, our findings demonstrate
that IL-2R is an absolute requirement for the development of the
regulatory CD25+CD4+ T cells that control
peripheral CD4 T cell homeostasis, while IL-2 is required for
establishing a sizeable population of these cells in the peripheral
pools.
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M. Fujimoto, H. Tsutsui, O. Xinshou, M. Tokumoto, D. Watanabe, Y. Shima, T. Yoshimoto, H. Hirakata, I. Kawase, K. Nakanishi, et al. Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases Int. Immunol., February 1, 2004; 16(2): 303 - 314. [Abstract] [Full Text] [PDF]
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 S. Xiao, S.-s. J. Sung, S. M. Fu, and S.-T. Ju Combining Fas Mutation with Interleukin-2 Deficiency Prevents Colitis and Lupus: IMPLICATING INTERLEUKIN-2 FOR AUTO-REACTIVE T CELL EXPANSION AND Fas LIGAND FOR COLON EPITHELIAL CELL DEATH J. Biol. Chem., December 26, 2003; 278(52): 52730 - 52738. [Abstract] [Full Text] [PDF]
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J. Ermann and C. G. Fathman Costimulatory signals controlling regulatory T cells PNAS, December 23, 2003; 100(26): 15292 - 15293. [Full Text] [PDF]
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 T. R. Malek The main function of IL-2 is to promote the development of T regulatory cells J. Leukoc. Biol., December 1, 2003; 74(6): 961 - 965. [Abstract] [Full Text]
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M. A. Burchill, C. A. Goetz, M. Prlic, J. J. O'Neil, I. R. Harmon, S. J. Bensinger, L. A. Turka, P. Brennan, S. C. Jameson, and M. A. Farrar Distinct Effects of STAT5 Activation on CD4+ and CD8+ T Cell Homeostasis: Development of CD4+CD25+ Regulatory T Cells versus CD8+ Memory T Cells J. Immunol., December 1, 2003; 171(11): 5853 - 5864. [Abstract] [Full Text] [PDF]
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Q. Tang, K. J. Henriksen, E. K. Boden, A. J. Tooley, J. Ye, S. K. Subudhi, X. X. Zheng, T. B. Strom, and J. A. Bluestone Cutting Edge: CD28 Controls Peripheral Homeostasis of CD4+CD25+ Regulatory T Cells J. Immunol., October 1, 2003; 171(7): 3348 - 3352. [Abstract] [Full Text] [PDF]
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A. Antov, L. Yang, M. Vig, D. Baltimore, and L. Van Parijs Essential Role for STAT5 Signaling in CD25+CD4+ Regulatory T Cell Homeostasis and the Maintenance of Self-Tolerance J. Immunol., October 1, 2003; 171(7): 3435 - 3441. [Abstract] [Full Text] [PDF]
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H. von Boehmer Dynamics of Suppressor T Cells: In Vivo Veritas J. Exp. Med., September 15, 2003; 198(6): 845 - 849. [Full Text] [PDF]
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S. Fisson, G. Darrasse-Jeze, E. Litvinova, F. Septier, D. Klatzmann, R. Liblau, and B. L. Salomon Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State J. Exp. Med., September 2, 2003; 198(5): 737 - 746. [Abstract] [Full Text] [PDF]
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C. Asseman, S. Read, and F. Powrie Colitogenic Th1 Cells Are Present in the Antigen-Experienced T Cell Pool in Normal Mice: Control by CD4+ Regulatory T Cells and IL-10 J. Immunol., July 15, 2003; 171(2): 971 - 978. [Abstract] [Full Text] [PDF]
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T. Barthlott, G. Kassiotis, and B. Stockinger T Cell Regulation as a Side Effect of Homeostasis and Competition J. Exp. Med., February 17, 2003; 197(4): 451 - 460. [Abstract] [Full Text] [PDF]
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