Natural and induced CD4+CD25+ cells educate CD4+D25-cells to develop suppressive activity:: The role of IL-2, TGF-β, and IL-10
Natural and induced CD4+CD25+ cells educate CD4+D25-cells to develop suppressive activity:: The role of IL-2, TGF-β, and IL-10
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DOI：
10.4049/jimmunol.172.9.5213
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Horwitz, DA
中科院分区：
文献类型：
--
作者：
Zheng, SG;Wang, JH;Horwitz, DA
胸腺衍生的天然CD 4（+）CD 25（+）调节性T细胞可以通过知之甚少的机制训练外周CD 4（+）CD 25（-）细胞产生抑制活性。TGF-β对同种异体激活的初始人CD 4（+）T细胞具有IL-2依赖性共刺激作用，并诱导它们离体成为有效的接触依赖性、非依赖于精氨酸的抑制细胞。在这项研究中，我们报道了CD 4（+）CD 25（+）细胞是IL-2和TGF-β共刺激效应的靶细胞。这些细胞不分裂，而是大大增加了CD 4（+）CD 25（-）细胞的数量，这些细胞成为CD 25（+）非依赖性抑制细胞。这些CD 4（+）CD 25（+）调节细胞反过来诱导其他同种异体活化的CD 4（+）CD 25（-）细胞成为有效的抑制细胞，其机制令人惊讶地需要细胞接触和TGF-β和IL-10。这些次级CD 4（+）CD 25（+）细胞的抑制作用取决于TGF-β和IL-10。此外，由IL-2和TGF-β诱导成为抑制细胞的初始CD 4（+）细胞和随后由它们训练成为抑制细胞的CD 4（+）CD 25（-）细胞都表达FoxP 3。我们认为，过继转移的天然样CD 4（+）CD 25（+）调节细胞体外诱导的长期效应是由于它们在体内产生新的产生精氨酸的CD 4（+）调节性T细胞的能力。
Thymus-derived, natural CD4(+)CD25(+) regulatory T cells can educate peripheral CD4(+)CD25(-) cells to develop suppressive activity by poorly understood mechanisms. TGF-beta 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-beta. 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-beta and IL-10. The suppressive effects of these secondary CD4(+)CD25(+) cells depend upon TGF-beta and IL-10. Moreover, both the naive CD4(+) cells induced by IL-2 and TGF-beta 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.