Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Nature. 2011 Aug 14;477(7363):216-9. doi: 10.1038/nature10339.
Infections localized to peripheral tissues such as the skin result in the priming of T-cell responses that act to control pathogens. Activated T cells undergo migrational imprinting within the draining lymph nodes, resulting in memory T cells that provide local and systemic protection. Combinations of migrating and resident memory T cells have been implicated in long-term peripheral immunity, especially at the surfaces that form pathogen entry points into the body. However, T-cell immunity consists of separate CD4(+) helper T cells and CD8(+) killer T cells, with distinct effector and memory programming requirements. Whether these subsets also differ in their ability to form a migrating pool involved in peripheral immunosurveillance or a separate resident population responsible for local infection control has not been explored. Here, using mice, we show key differences in the migration and tissue localization of memory CD4(+) and CD8(+) T cells following infection of the skin by herpes simplex virus. On resolution of infection, the skin contained two distinct virus-specific memory subsets; a slow-moving population of sequestered CD8(+) T cells that were resident in the epidermis and confined largely to the original site of infection, and a dynamic population of CD4(+) T cells that trafficked rapidly through the dermis as part of a wider recirculation pattern. Unique homing-molecule expression by recirculating CD4(+) T effector-memory cells mirrored their preferential skin-migratory capacity. Overall, these results identify a complexity in memory T-cell migration, illuminating previously unappreciated differences between the CD4(+) and CD8(+) subsets.
定位于皮肤等外周组织的感染会引发 T 细胞反应，从而控制病原体。活化的 T 细胞在引流淋巴结中经历迁移印迹，形成提供局部和全身保护的记忆 T 细胞。迁移和驻留记忆 T 细胞的组合已被牵连到长期外周免疫中，特别是在形成病原体进入身体的途径的表面。然而，T 细胞免疫由独立的 CD4(+)辅助 T 细胞和 CD8(+)杀伤 T 细胞组成，具有不同的效应器和记忆编程要求。这些亚群在形成参与外周免疫监视的迁移池的能力方面是否也存在差异，或者在负责局部感染控制的独立驻留群体中是否存在差异，尚未得到探索。在这里，我们使用小鼠表明，单纯疱疹病毒感染皮肤后，记忆 CD4(+)和 CD8(+) T 细胞的迁移和组织定位存在关键差异。感染消退后，皮肤包含两种不同的病毒特异性记忆亚群；一种是缓慢移动的隔离 CD8(+)T 细胞群，它们存在于表皮中，主要局限于原始感染部位，另一种是快速流动的 CD4(+)T 细胞群，作为更广泛的再循环模式的一部分，快速穿过真皮。循环中的 CD4(+)T 效应记忆细胞独特的归巢分子表达反映了它们优先的皮肤迁移能力。总体而言，这些结果揭示了记忆 T 细胞迁移的复杂性，阐明了 CD4(+)和 CD8(+)亚群之间以前未被重视的差异。
