IL-2 is essential for TGF-β to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells
IL-2 is essential for TGF-β to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells
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DOI：
10.4049/jimmunol.178.4.2018
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发表时间：
2007-02-15
影响因子：
4.4
通讯作者：
Horwitz, David A.
中科院分区：
文献类型：
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作者：
Zheng, Song Guo;Wang, Juhua;Horwitz, David A.
IL-2和tgf - β在诱导和维持免疫耐受中都有重要作用，但这些细胞因子是单独作用还是共同作用来实现这一作用尚不清楚。虽然其他研究报道IL-2可以直接通过天然CD4(+)CD25（+）调节性T细胞增强叉头盒蛋白P3 （Foxp3）转录因子的表达，但在本研究中，我们报道IL-2对外周调节性CD4（+）细胞产生的作用是间接的。Ab中和研究和IL-2缺陷小鼠实验表明，tgf - β需要IL-2才能诱导初始CD4(+)CD25（-）细胞转变为CD25（+）并表达Foxp3，并发展出CD4(+)CD25（+）调节细胞的特征。IL-2对这些适应性Foxp3（+）调节细胞的产生和扩增的影响不是多余的，但IL-4、IL-7和IL-15，其他常见的γ链细胞因子，可以维持Foxp3的表达。由于自身免疫性疾病患者通常在产生IL-2和/或tgf - β方面存在缺陷，因此体外产生带有这些细胞因子的自体T调节细胞并在体内转移可能具有相当大的治疗潜力。中华免疫学杂志，2007,18(8):2018-2027。
IL-2 and TGF-beta both have important roles in the induction and maintenance of immunologic tolerance, but whether these cytokines act separately or together to achieve this effect is poorly understood. Although others have reported that IL-2 can directly enhance forkhead box protein P3 (Foxp3) transcription factor expression by natural CD4(+)CD25(+) regulatory T cells, in this study, we report that the role of IL-2 on the generation of peripheral regulatory CD4(+) cells is indirect. Ab neutralization studies and experiments with IL-2-deficient mice have revealed that IL-2 is required for TGF-beta to induce naive CD4(+)CD25(-) cells to become CD25(+) and express Foxp3, and develop the characteristic properties of CD4(+)CD25(+) regulatory cells. This effect of IL-2 on the generation and expansion of these adaptive Foxp3(+) regulatory cells is nonredundant, but IL-4, IL-7, and IL-15, other common gamma-chain cytokines, could sustain Foxp3 expression. Because subjects with autoimmune diseases often have defects in the production of IL-2 and/or TGF-beta, the generation of autologous T regulatory cells ex vivo with these cytokines for transfer in vivo may have considerable therapeutic potential. The Journal of Immunology, 2007, 178: 2018-2027.