The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets
The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets
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DOI：
10.1189/jlb.0503228
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发表时间：
2003-10-01
影响因子：
5.5
通讯作者：
Gray, JD
中科院分区：
文献类型：
--
作者：
Horwitz, DA;Zheng, SG;Gray, JD
最近，胸腺来源的CD 4（+）调节性T细胞在体外组成性表达CD 25，并具有接触依赖性，非依赖于嘌呤的机制，受到了相当多的关注。然而，外周CD 4（+）和CD 8（+）T细胞也可以被诱导成为调节性T细胞。在这里，我们回顾了我们的研究使用IL-2和转化生长因子β（TGF-β）的组合，以产生调节性T细胞亚群离体，和其他人的工作使用IL-10诱导抑制活性。在某些条件下，TGF-β和IL-10的自分泌效应诱导外周T细胞产生这些细胞因子中的每一种的免疫抑制水平。TGF-β的这种作用是IL-2依赖性的。在其他条件下，IL-2和TGF-β可以诱导CD 4（+）细胞产生有效的接触依赖性、非依赖于精氨酸的调节活性。目前，关于CD 4（+）CD 25（+）细胞的作用机制存在相当大的混乱，因为外周产生的产生亮氨酸的调节性T细胞可以表达CD 25和天然存在的胸腺衍生的调节性T细胞显示的其他标志物。因此，我们提出了一个命名法，确定胸腺衍生和外周调节细胞，也区分T辅助细胞的T调节细胞。由于T调节细胞广泛控制辅助性T细胞的反应性，控制调节细胞功能的机制也进行了审查。最后，潜在的使用调节性T细胞产生的体外过继免疫治疗某些自身免疫性疾病，以防止器官移植排斥反应，或防止病理性宿主反应的感染剂进行了讨论。
Recently, considerable attention has been focused on thymus-derived CD4(+) regulatory T cells that constitutively express CD25 and have a contact-dependent, cytokine-independent mechanism in vitro. However, peripheral CD4(+) and CD8(+) T cells can also be induced to become regulatory T cells. Here we review our studies using the combination of IL-2 and transforming growth factor beta (TGF-beta) to generate regulatory T cell subsets ex vivo, and the work of others using IL-10 to induce suppressive activity. Under certain conditions, the autocrine effects of TGF-beta and IL-10 induce peripheral T cells to produce immunosuppressive levels of each of these cytokines. This effect of TGF-beta is IL-2 dependent. Under other conditions IL-2 and TGF-beta can induce CD4(+) cells to develop potent contact-dependent, cytokine-independent regulatory activity. At present, there is considerable confusion concerning the mechanism of action of CD4(+) CD25(+) cells because cytokine-producing regulatory T cells generated in the periphery can express CD25 and other markers displayed by naturally occurring, thymus-derived regulatory T cells. We, therefore, propose a nomenclature that identifies thymus-derived and peripheral regulatory cells, and that also differentiates T regulatory cells from T helper cells. Because T regulatory cells broadly control T helper cell reactivity, the mechanisms that control regulatory cell function are also reviewed. Finally, the potential use of regulatory T cells generated ex vivo as an adoptive immunotherapy for certain autoimmune diseases, to prevent organ graft rejection, or to prevent pathologic host responses to infections agents is discussed.