Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners
Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners
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DOI：
10.1016/j.bbrc.2012.12.125
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发表时间：
2013-02-08
影响因子：
3.1
通讯作者：
Ono, Kazuhisa
中科院分区：
文献类型：
--
作者：
Takaoka, Yuki;Kawamoto, Seiji;Ono, Kazuhisa
诱导抗DNA或组蛋白的抗核抗体是自身免疫性疾病的一个标志，但它们对疾病易感性的实际贡献仍有待澄清。我们之前报道过，在大鼠耐受性肝移植模型中，抗组蛋白H1的自身抗体是一个关键的移植物存活因子。在这里，我们展示了一种免疫抑制抗组蛋白H1单克隆抗体（anti-H1 mAb）直接作用于T细胞，以抑制它们对T细胞受体（TCR）连接的激活。有趣的是，在次优剂量下，抗h1单抗的T细胞活化抑制活性需要调节性T细胞（Treg），而高剂量的抗h1单抗刺激会触发Treg细胞独立的，直接负调控T细胞在TCR交联时的活化。在Treg细胞依赖的免疫抑制作用模式下，anti-H1 mAb并不诱导CD4(+-) Foxp3(+) Treg细胞的扩增，而是增强了它们的调节能力。这些结果揭示了以前未被认识到的抗h1自身抗体的T细胞调节作用，其过量产生通常被认为是自身免疫设置的致病性。(C) 2013爱思唯尔公司版权所有。
Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4(+-) Foxp3(+) Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings. (C) 2013 Elsevier Inc. All rights reserved.