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, and IL-101
Division of Rheumatology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033
Thymus-derived, natural CD4+CD25+ regulatory T cells can educate peripheral CD4+CD25– cells to develop suppressive activity by poorly understood mechanisms. TGF-
has IL-2-dependent costimulatory effects on alloactivated naive, human CD4+ T cells and induces them ex vivo to become potent contact-dependent, cytokine-independent suppressor cells. In this study, we report that CD4+CD25+ cells are the targets of the costimulatory effects of IL-2 and TGF-. These cells do not divide, but, instead, greatly increase the numbers of CD4+CD25– cells that become CD25+ cytokine-independent suppressor cells. These CD4+CD25+ regulatory cells, in turn, induce other alloactivated CD4+CD25– cells to become potent suppressor cells by mechanisms that, surprisingly, require both cell contact and TGF- and IL-10. The suppressive effects of these secondary CD4+CD25+ cells depend upon TGF- and IL-10. Moreover, both the naive CD4+ cells induced by IL-2 and TGF- to become suppressor cells, and the subsequent CD4+CD25– cells educated by them to become suppressors express FoxP3. We suggest that the long-term effects of adoptively transferred natural-like CD4+CD25+ regulatory cells induced ex vivo are due to their ability to generate new cytokine-producing CD4+ regulatory T cells in vivo.
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M. A. Curotto de Lafaille, A. C. Lino, N. Kutchukhidze, and J. J. Lafaille CD25- T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion J. Immunol., December 15, 2004; 173(12): 7259 - 7268. [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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