Cottalorda Anne, Mercier Blandine C, Mbitikon-Kobo Florentin M, Arpin Christophe, Teoh Denise Y L, McMichael Andrew, Marvel Jacqueline, Bonnefoy-Bérard Nathalie
Université de Lyon, Lyon, France.
Eur J Immunol. 2009 Oct;39(10):2673-81. doi: 10.1002/eji.200939627.
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.
已知记忆性CD8(+) T细胞的持久性在很大程度上受常见γ链细胞因子控制，如白细胞介素-2（IL-2）、白细胞介素-7（IL-7）和白细胞介素-15（IL-15）。然而，其他分子可能也参与了这一现象。我们在此表明，与野生型小鼠相比，Toll样受体2（TLR2）基因敲除小鼠的记忆表型CD8(+) T细胞频率降低。这促使我们研究TLR2在记忆性CD8(+) T细胞稳态中的作用。我们在此描述了一种新的依赖TLR2的机制，在缺乏特异性抗原的情况下，该机制直接控制记忆性CD8(+) T细胞的增殖和γ干扰素（IFN-γ）分泌。我们证明，在体外和体内，记忆性CD8(+) T细胞上的TLR2激活均能增加由IL-7诱导的其增殖和扩增。我们还表明，TLR2配体在体外与IL-2协同作用以诱导IFN-γ分泌。这两个结论均在自发产生的记忆表型和抗原特异性记忆性CD8(+) T细胞中得到。总之，我们的数据支持这样一种观点，即响应微生物刺激或内源性危险信号的持续TLR2信号传导可能直接有助于维持机体中记忆性CD8(+) T细胞的多样性。
