Pace Luigia, Pioli Claudio, Doria Gino
Laboratory of Immunology, Department of Biology, University of Rome Tor Vergata, Italy.
J Immunol. 2005 Jun 15;174(12):7645-53. doi: 10.4049/jimmunol.174.12.7645.
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.
将小鼠CD4(+)CD25(+)调节性T（Treg）细胞与CD4(+)CD25(-)辅助性T（Th）细胞及抗原呈递细胞（APC）或纯化的B细胞共培养，并用抗CD3单克隆抗体刺激。用B细胞替代APC对CD4(+)CD25(-) Th细胞的抑制作用无显著影响。当向单独的细胞群体中添加白细胞介素-4（IL-4）时，这种细胞因子可促进CD4(+)CD25(-) Th细胞和CD4(+)CD25(+) Treg细胞增殖，而CD4(+)CD25(+) Treg细胞的抑制能力得以保留。相反，添加到APC、CD4(+)CD25(-) Th细胞和CD4(+)CD25(+) Treg细胞共培养体系中的IL-4，通过诱导Bcl-2表达促进CD4(+)CD25(-) Th细胞存活，从而抑制了CD4(+)CD25(+) Treg细胞对CD4(+)CD25(-) Th细胞的抑制作用。不同的是，添加IL-13对抑制作用无影响，尽管该细胞因子与IL-4共用一条受体链。当用Th1和Th2细胞替代初始CD4(+)CD25(-) Th细胞时，两个亚群的细胞增殖均受到同等程度的抑制，但与CD4(+)CD25(-) Th细胞相比，抑制作用较弱。Th2细胞产生IL-4的能力也受到抑制。这些结果表明，尽管CD4(+)CD25(+) Treg细胞抑制IL-4的产生，但添加IL-4可通过促进CD4(+)CD25(-) Th细胞存活和增殖来抵消CD4(+)CD25(+) Treg细胞介导的抑制作用。
