CD4+CD25+ T regulatory cells activated during feline immunodeficiency virus infection convert T helper cells into functional suppressors through a membrane-bound TGFβ / GARP-mediated mechanism.
CD4+CD25+ T regulatory cells activated during feline immunodeficiency virus infection convert T helper cells into functional suppressors through a membrane-bound TGFβ / GARP-mediated mechanism.
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DOI：
10.1186/1743-422x-11-7
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发表时间：
2014-01-18
期刊：
影响因子：
4.8
通讯作者：
Fogle JE
中科院分区：
文献类型：
--
作者：
Miller MM;Petty CS;Tompkins MB;Fogle JE
我们和其他人以前曾报道，活化的T调节细胞（Treg）上的细胞膜结合TGFβ（mTGFβ）介导抑制功能。目前的研究结果表明，一种称为糖蛋白A重复占主导地位（GARP）的新型蛋白质将mTGFβ锚定在Treg细胞表面并促进抑制活性。最近，我们描述了GARP+TGFβ+ Treg细胞在FIV感染过程中扩增。由于Treg细胞是无反应性的，并且通常表现出较差的增殖能力，因此我们询问在猫免疫缺陷病毒（FIV）感染过程中Treg稳态是如何维持的。在这里，我们报告了来自FIV+猫的Treg细胞表达GARP和mTGFβ，并将T辅助细胞（Th）转化为表型和功能性Treg细胞。通过Treg细胞的抗TGF β或抗GARP处理或通过Th细胞的抗TGF βRII处理消除Th向Treg的转化，表明从Th库募集Treg细胞是由TGFβ/TGFβRII信号传导介导的，并且细胞表面GARP在该过程中起主要作用。这些研究结果表明，Th到Treg的转换可能会引发一系列事件，这些事件有助于维持病毒库，进行性Th细胞免疫抑制和免疫缺陷的发展，所有这些都是艾滋病慢病毒感染发病机制的核心。
We and others have previously reported that cell membrane-bound TGFβ (mTGFβ) on activated T regulatory (Treg) cells mediates suppressor function. Current findings suggest that a novel protein known as Glycoprotein A Repetitions Predominant (GARP) anchors mTGFβ to the Treg cell surface and facilitates suppressor activity. Recently, we have described that GARP+TGFβ+ Treg cells expand during the course of FIV infection. Because Treg cells are anergic and generally exhibit poor proliferative ability, we asked how Treg homeostasis is maintained during the course of feline immunodeficiency virus (FIV) infection. Here, we report that Treg cells from FIV+ cats express GARP and mTGFβ and convert T helper (Th) cells into phenotypic and functional Treg cells. Th to Treg conversion was abrogated by anti-TGFβ or anti-GARP treatment of Treg cells or by anti-TGFβRII treatment of Th cells, suggesting that Treg cell recruitment from the Th pool is mediated by TGFβ/TGFβRII signaling and that cell-surface GARP plays a major role in this process. These findings suggest Th to Treg conversion may initiate a cascade of events that contributes to the maintenance of virus reservoirs, progressive Th cell immunosuppression, and the development of immunodeficiency, all of which are central to the pathogenesis of AIDS lentivirus infections.