Murine CD4+CD25+ T regulatory (Treg) cells were cocultured with CD4+CD25- Th cells and APCs or purified B cells and stimulated by anti-CD3 mAb. Replacement of APCs by B cells did not significantly affect the suppression of CD4+CD25- Th cells. When IL-4 was added to separate cell populations, this cytokine promoted CD4+CD25- Th and CD4+CD25+ Treg cell proliferation, whereas the suppressive competence of CD4+CD25 + Treg cells was preserved. Conversely, IL-4 added to coculture of APCs, CD4+CD25- Th cells, and CD4+CD25 + Treg cells inhibited the suppression of CD4+CD25 - Th cells by favoring their survival through the induction of Bcl-2 expression. At variance, suppression was not affected by addition of IL-13, although this cytokine shares with IL-4 a receptor chain. When naive CD4 +CD25- Th cells were replaced by Th1 and Th2 cells, cell proliferation of both subsets was equally suppressed, but suppression was less pronounced compared with that of CD4+CD25- Th cells. IL-4 production by Th2 cells was also inhibited. These results indicate that although CD4+CD25+ Treg cells inhibit IL-4 production, the addition of IL-4 counteracts CD4+CD25+ Treg cell-mediated suppression by promoting CD4+CD25- Th cell survival and proliferation. Copyright © 2005 by The American Association of Immunologists, Inc.

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