CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production
CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production
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DOI：
10.1172/jci40178
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发表时间：
2010-01-01
影响因子：
15.9
通讯作者：
Borst, Jannie
中科院分区：
文献类型：
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作者：
Peperzak, Victor;Xiao, Yanling;Borst, Jannie
对感染的免疫依赖于CD 8（+）T细胞的克隆扩增，它们作为效应CTL的维持，以及它们被选择进入记忆群体。这些过程依赖于向活化的CD 8（+）T细胞传递生存信号。我们在此揭示了共刺激CD 27-CD 70相互作用维持CD 8（+）效应T细胞在感染组织中存活的机制。通过无偏的全基因组基因表达分析，我们确定了IL 2基因是小鼠CD 8（+）T细胞中最突出的CD 27靶基因。在体外，CD 27通过IL-2依赖性存活信号引导IL-2表达并促进致敏的CD 8 + T细胞的克隆扩增。在鼻内感染流感病毒的小鼠中，Cd 27（-/-）CD 8（+）效应T细胞显示IL-2产生减少，伴随着淋巴器官和肺（构成组织效应部位）中蓄积受损。用IL 2基因重建Cd 27（-/-）CD 8（+）T细胞使其在肺中的积累恢复到野生型水平，但不能挽救其在淋巴器官中的积累。竞争实验表明，在CD 27控制下产生的IL-2以自分泌方式支持效应CD 8（+）T细胞在肺中的存活。我们的结论是，CD 27信号指导IL-2的生产，据报道是必不可少的，以维持生存的病毒特异性CTL在非淋巴组织。
Immunity to infections relies on clonal expansion of CD8(+) T cells, their maintenance as effector CTLs, and their selection into a memory population. These processes rely on delivery of survival signals to activated CD8(+) T cells. We here reveal the mechanism by which costimulatory CD27-CD70 interactions sustain survival of CD8(+) effector T cells in infected tissue. By unbiased genome-wide gene expression analysis, we identified the Il2 gene as the most prominent CD27 target gene in murine CD8(+) T cells. In vitro, CD27 directed IL-2 expression and promoted clonal expansion of primed CD8+ T cells exclusively by IL-2-dependent survival signaling. In mice intranasally infected with influenza virus, Cd27(-/-) CD8(+) effector T cells displayed reduced IL-2 production, accompanied by impaired accumulation in lymphoid organs and in the lungs, which constitute the tissue effector site. Reconstitution of Cd27(-/-) CD8(+) T cells with the IL2 gene restored their accumulation to wild-type levels in the lungs, but it did not rescue their accumulation in lymphoid organs. Competition experiments showed that the IL-2 produced under the control of CD27 supported effector CD8(+) T cell survival in the lungs in an autocrine manner. We conclude that CD27 signaling directs the IL-2 production that is reportedly essential to sustain survival of virus-specific CTLs in nonlymphoid tissue.