Local antigen in nonlymphoid tissue promotes resident memory CD8+ T cell formation during viral infection.
Local antigen in nonlymphoid tissue promotes resident memory CD8+ T cell formation during viral infection.
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非淋巴组织中的局部抗原促进了病毒感染期间居民记忆CD8+ T细胞的形成。
DOI：
10.1084/jem.20151855
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发表时间：
2016-05-30
期刊：
影响因子：
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通讯作者：
Nolz JC
中科院分区：
文献类型：
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作者：
Khan TN;Mooster JL;Kilgore AM;Osborn JF;Nolz JC
病毒感染期间激活的 CD8+ T 细胞以不依赖于抗原的方式迁移到受感染的皮肤。抗原的局部识别驱动分化为 Trm CD8+ T 细胞。组织驻留记忆 (Trm) CD8+ T 细胞在功能上与其循环对应细胞不同，并且是宿主防止再感染的有效介质。感染过程中非淋巴组织中抗原的局部识别是否会影响 Trm 群体的形成仍有待解决。使用表达模型抗原的牛痘病毒 (VacV) 皮肤感染，我们发现局部抗原识别对 Trm 形成具有深远影响。激活的 CD8+ T 细胞以炎症依赖性但不依赖于抗原的方式运输到 VacV 感染的皮肤。然而，病毒清除后，当组织微环境中存在抗原时，Trm 形成随后增加约 50 倍。非淋巴组织中的二次抗原刺激导致 CD8+ T 细胞快速表达 CD69 并保留在感染部位。最后，在 VacV 感染过程中以抗原依赖性方式形成的 Trm CD8+ T 细胞成为皮肤局部抗原特异性炎症反应的有效刺激剂。因此，我们的研究表明，非淋巴组织微环境中抗原的存在在功能性 Trm CD8+ T 细胞群的形成中起着关键作用，这一发现与疫苗设计和炎症性疾病的预防相关。
CD8+ T cells activated during viral infection migrate to infected skin in an antigen-independent manner. Local recognition of antigens drives the differentiation into Trm CD8+ T cells. Tissue-resident memory (Trm) CD8+ T cells are functionally distinct from their circulating counterparts and are potent mediators of host protection against reinfection. Whether local recognition of antigen in nonlymphoid tissues during infection can impact the formation of Trm populations remains unresolved. Using skin infections with vaccinia virus (VacV)–expressing model antigens, we found that local antigen recognition had a profound impact on Trm formation. Activated CD8+ T cells trafficked to VacV-infected skin in an inflammation-dependent, but antigen-independent, manner. However, after viral clearance, there was a subsequent ∼50-fold increase in Trm formation when antigen was present in the tissue microenvironment. Secondary antigen stimulation in nonlymphoid tissue caused CD8+ T cells to rapidly express CD69 and be retained at the site of infection. Finally, Trm CD8+ T cells that formed during VacV infection in an antigen-dependent manner became potent stimulators of localized antigen-specific inflammatory responses in the skin. Thus, our studies indicate that the presence of antigen in the nonlymphoid tissue microenvironment plays a critical role in the formation of functional Trm CD8+ T cell populations, a finding with relevance for both vaccine design and prevention of inflammatory disorders.