CD30 Discriminates Heat Shock Protein 60-Induced FOXP3+ CD4+ T Cells with a Regulatory Phenotype
CD30 Discriminates Heat Shock Protein 60-Induced FOXP3+ CD4+ T Cells with a Regulatory Phenotype
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DOI：
10.4049/jimmunol.0901901
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发表时间：
2010-08-15
影响因子：
4.4
通讯作者：
Prakken, Berent
中科院分区：
文献类型：
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作者：
de Kleer, Isme;Vercoulen, Yvonne;Prakken, Berent
在许多动物模型中，炎性疾病的表现可以通过过继转移CD 4（+）FOXP 3（+）调节性T细胞（TCFs）来预防。CD 4（+）FOXP 3（+）Treg可以通过分离和扩增多克隆天然存在的Treg或通过CD 4（+）CD 25（-）FOXP 3（-）T细胞的Ag特异性激活来获得。两个主要障碍阻碍了将后一种方案转化为治疗应用。首先，缺乏对相关自身抗原的了解。第二，所得到的群体被活化的CD 4（+）T细胞污染，所述活化的CD 4（+）T细胞瞬时表达叉头盒P3但不获得调节功能。因此，这些细胞对于临床应用可能不安全。在这项研究中，我们证明，高度抑制FOXP 3（+）T细胞活化的CD 4（+）CD 25（-）T细胞与自身抗原的人60 kDa热休克蛋白（HSP 60）可以在体外诱导。活化诱导的抑制性FOXP 3（+）T细胞可以通过CD 30的表面表达与非抑制性FOXP 3（+）效应细胞区分。我们证实，诱导的CD 30（+）FOXP 3（+）Tclase识别HSP 60表位，并且通过APC上的TLR 4信号传导增强HSP 60对Tclase的诱导。这些发现对产生和分离纯的Ag特异性T细胞群具有意义，具有预防和治疗人类炎症性疾病的潜力。免疫学杂志，2010，185：2071-2079。
In many animal models, the manifestations of inflammatory diseases can be prevented by the adoptive transfer of CD4(+)FOXP3(+) regulatory T cells (Tregs). CD4(+)FOXP3(+) Tregs can be obtained by isolation and expansion of polyclonal naturally occurring Tregs or by Ag-specific activation of CD4(+)CD25(-)FOXP3(-) T cells. Two major obstacles are hampering the translation of this latter protocol into therapeutic application. First, there is a lack of knowledge on relevant autoantigens. Second, the resulting population is contaminated with activated CD4(+) T cells that transiently express Forkhead box P3 but gain no regulatory function. Therefore, these cells may not be safe for clinical application. In this study, we demonstrate that highly suppressive FOXP3(+) Tregs can be induced in vitro by the activation of CD4(+)CD25(-) T cells with the self-Ag human 60-kDa heat shock protein (HSP60). The activation induced suppressive FOXP3(+) Tregs can be distinguished by surface expression of CD30 from nonsuppressive FOXP3(+) effector cells. We confirm that the induced CD30(+)FOXP3(+) Tregs recognize HSP60 epitopes and that the induction of Tregs by HSP60 is enhanced by signaling via TLR4 on APCs. These findings have implications for the generation and isolation of pure populations of Ag-specific Tregs, with the potential to prevent and treat human inflammatory diseases. The Journal of Immunology, 2010, 185: 2071-2079.