Autoantigen-specific TGFβ-Induced Foxp3+ regulatory T cells prevent Autoimmunity by inhibiting dendritic cells from activating autoreactive T cells
Autoantigen-specific TGFβ-Induced Foxp3+ regulatory T cells prevent Autoimmunity by inhibiting dendritic cells from activating autoreactive T cells
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DOI：
10.4049/jimmunol.179.7.4685
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Shevach, Ethan M.
中科院分区：
文献类型：
--
作者：
DiPaolo, Richard J.;Brinster, Carine;Shevach, Ethan M.
正在设计几种策略来测试Ag特异性调节性T细胞预防或治疗自身免疫性疾病的治疗潜力。在这项研究中，我们证明了对天然表达的自身抗原（H+/K+ ATP酶）具有特异性的幼稚CD 4（+）Foxp 3（-）T细胞在TGF β存在下刺激时可以转化为Foxp 3（+）T调节细胞（T细胞）。TGF β诱导的T细胞（iT细胞）具有体外天然产生的调节性T细胞的所有特征，更重要的是，在自身免疫性胃炎的小鼠模型中有效预防器官特异性自身免疫。H ~+/K ~+ ATP酶特异性iTcl 4能抑制自身反应性T细胞的初始启动和增殖，并且似乎通过作用于H ~+/K ~+ ATP酶呈递树突状细胞（DC）来实现。在体内暴露于iT细胞的DC刺激H+/K+ ATP酶特异性T细胞增殖和细胞因子产生的能力降低。在体外，iTl 4特异性地降低呈递DC的H+/K+ ATP酶表面上的CD 80和CD 86的表达。这些研究揭示了Ag特异性iT细胞预防自身免疫的治疗潜力，并提供了一种机制，通过该机制，调节性T细胞群体以及可能的其他细胞在体内介导其抑制作用。
Several strategies are being designed to test the therapeutic potential of Ag-specific regulatory T cells to prevent or treat autoimmune diseases. In this study, we demonstrate that naive CD4(+)Foxp3(-) T cells specific for a naturally expressed autoantigen (H+/K+ ATPase) can be converted to Foxp3(+) T regulatory cells (Tregs) when stimulated in presence of TGF beta. TGF beta-induced Tregs (iTregs) have all the characteristics of naturally generated regulatory T cells in vitro, and more importantly, are effective at preventing organ-specific autoimmunity in a murine model of autoimmune gastritis. H+/K+ ATPase specific iTregs were able to inhibit the initial priming and proliferation of autoreactive T cells, and appear to do so by acting on H+/K+ ATPase presenting dendritic cells (DC). DC exposed to iTregs in vivo were reduced in their ability to stimulate proliferation and cytokine production by H+/K+ ATPase specific T cells. iTregs specifically reduced CD80 and CD86 expression on the surface of H+/K+ ATPase presenting DC in vitro. These studies reveal the therapeutic potential of Ag specific iTregs to prevent autoimmunity, and provide a mechanism by which this population of regulatory T cells, and perhaps others, mediate their suppressive effects in vivo.