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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 …