TLR2 engagement on memory CD8+ T cells improves their cytokine-mediated proliferation and IFN-γ secretion in the absence of Ag
TLR2 engagement on memory CD8+ T cells improves their cytokine-mediated proliferation and IFN-γ secretion in the absence of Ag
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DOI：
10.1002/eji.200939627
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Bonnefoy-Berard, Nathalie
中科院分区：
文献类型：
--
作者：
Cottalorda, Anne;Mercier, Blandine C.;Bonnefoy-Berard, Nathalie
已知记忆性CD 8（+）T细胞的持久性在很大程度上受常见的γ链细胞因子如IL-2、IL-7和IL-15控制。然而，其他分子可能参与这种现象。我们在这里显示，与WT小鼠相比，TLR 2（-/-）小鼠的记忆表型CD 8（+）T细胞的频率降低。这促使我们研究TLR 2在记忆性CD 8（+）T细胞稳态中的作用。我们在这里描述了一种新的TLR 2依赖性机制，在没有特异性抗原的情况下，直接控制记忆性CD 8（+）T细胞增殖和IFN-γ分泌。我们证明，TLR 2参与记忆CD 8（+）T细胞增加其增殖和扩增诱导IL-7在体外和体内。我们还表明，TLR 2配体与IL-2协同作用，在体外诱导IFN-γ分泌。这两个结论都是通过自发产生的记忆表型和抗原特异性记忆CD 8（+）T细胞获得的。总之，我们的数据支持这样的想法，即响应微生物刺激或内源性危险信号的连续TLR 2信号可能直接有助于维持生物体中的多样性记忆CD 8（+）T细胞。
Persistence of memory CD8(+) T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2(-/-) mice have a decreased frequency of memory phenotype CD8(+) T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8(+) T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8(+) T-cell proliferation and IFN-gamma secretion. We demonstrate that TLR2 engagement on memory CD8(+) T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-gamma secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8(+) T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8(+) T cells in the organism.