Recurrent superantigen exposure in vivo leads to highly suppressive CD4+CD25+ and CD4+CD25- T cells with anergic and suppressive genetic signatures.
Recurrent superantigen exposure in vivo leads to highly suppressive CD4+CD25+ and CD4+CD25- T cells with anergic and suppressive genetic signatures.
复制标题
体内反复接触超抗原会导致高度抑制的 CD4 CD25 和 CD4 CD25-T 细胞具有无能和抑制性遗传特征。
DOI：
10.1111/j.1365-2249.2008.03827.x
复制
发表时间：
2009
影响因子：
4.6
通讯作者：
Seroogy,CM
中科院分区：
文献类型：
--
作者：
Schartner,JM;Singh,AM;Dahlberg,PE;Nettenstrom,L;Seroogy,CM
葡萄球菌肠毒素B （SEB）通过T细胞受体的非规范信号激活T细胞，是体内T细胞无反应的一种已建立的模型。在这项研究中，我们试图描述seb暴露的CD4+T细胞的抑制特性，并将其与能量和抑制的遗传特征联系起来。seb暴露的CD25+和CD25- v β8+CD4+T细胞表达叉头盒P3 （FoxP3）的水平与初始CD25+T调节细胞相当，并且在体内暴露后富集。淋巴细胞能量相关基因（GRAIL）是一种与能量相关的E3泛素连接酶，在seb暴露的CD25+、CD25- foxp3 +Vβ8+CD4+T细胞和FoxP3-CD25-Vβ8+CD4+T细胞中表达上调，提示GRAIL可能在显性和隐性耐受中起重要作用。暴露于SEB的FoxP3+GRAIL+T细胞具有高度抑制性和非增殖性，不依赖于CD25表达水平，并通过糖皮质激素诱导的肿瘤坏死因子r相关蛋白独立机制，而在体外，初始T调节细胞在SEB激活下具有非抑制性和部分增殖性。最后，对传统T细胞的过继性转移表明，FoxP3+调节细胞在该模型系统中无法诱导。这些数据为慢性非规范T细胞受体参与导致高度抑制FoxP3+GRAIL+CD4+T细胞提供了一个新的范例。
Staphylococcal enterotoxin B (SEB) activates T cells via non-canonical signalling through the T cell receptor and is an established model for T cell unresponsivenessin vivo. In this study, we sought to characterize the suppressive qualities of SEB-exposed CD4+T cells and correlate this with genetic signatures of anergy and suppression. SEB-exposed CD25+and CD25-Vβ8+CD4+T cells expressed forkhead box P3 (FoxP3) at levels comparable to naive CD25+T regulatory cells and were enriched after exposurein vivo. Gene related to anergy in lymphocytes (GRAIL), an anergy-related E3 ubiquitin ligase, was up-regulated in the SEB-exposed CD25+and CD25-FoxP3+Vβ8+CD4+T cells and FoxP3-CD25-Vβ8+CD4+T cells, suggesting that GRAIL may be important for dominant and recessive tolerance. The SEB-exposed FoxP3+GRAIL+T cells were highly suppressive and non-proliferative independent of CD25 expression level and via a glucocorticoid-induced tumour necrosis factor R-related protein-independent mechanism, whereas naive T regulatory cells were non-suppressive and partially proliferative with SEB activationin vitro. Lastly, adoptive transfer of conventional T cells revealed that induction of FoxP3+regulatory cells is not operational in this model system. These data provide a novel paradigm for chronic non-canonical T cell receptor engagement leading to highly suppressive FoxP3+GRAIL+CD4+T cells.