Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation.
Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation.
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DOI：
10.1038/ncomms11514
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发表时间：
2016-05-10
影响因子：
16.6
通讯作者：
Carbone FR
中科院分区：
文献类型：
--
作者：
Collins N;Jiang X;Zaid A;Macleod BL;Li J;Park CO;Haque A;Bedoui S;Heath WR;Mueller SN;Kupper TS;Gebhardt T;Carbone FR
尽管屏障组织内的记忆T细胞可以作为永久居民持续存在，但至少会与血液进行一些交换。这种情况发生的程度尚不清楚。在这里，我们表明小鼠皮肤中的记忆 CD4+ T 细胞与稳态循环处于平衡状态。这些细胞分散在真皮的毛囊间区域，并与毛囊周围的抗原呈递细胞形成簇。感染或施用接触致敏剂后，皮肤 CD4+ T 细胞含量持续增加，仅限于细胞簇，同时 CCL5 依赖性 CD4+ T 细胞募集增加。皮肤 CCL5 源自 CD11b+ 细胞和 CD8+ T 细胞，消除后者会减少 CD4+ T 细胞数量。这些结果揭示了皮肤中 CD4+ 记忆 T 细胞的组织保留和平衡的复杂模式，该模式会因感染和炎症史而改变。 记忆 T 细胞是皮肤炎症的重要反应者，但细胞定位和与血液交换的动态尚不清楚。在这里，作者使用联体共生和活体显微镜显示 CD4+ 记忆 T 细胞与循环平衡并聚集在毛囊周围，以响应对病毒感染或接触致敏的 CCL5 依赖性反应。
Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4+ T cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4+ T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4+ T-cell recruitment. Skin CCL5 is derived from CD11b+ cells and CD8+ T cells, with the elimination of the latter decreasing CD4+ T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4+ memory T cells in skin, which is altered by infection and inflammation history. Memory T cells are vital responders to skin inflammation, but cell localization and dynamics of exchange with the bloodstream are not clear. Here the authors use parabiosis and intravital microscopy to show that CD4+ memory T cells equilibrate with the circulation and cluster around hair follicles in response to CCL5-dependent responses to viral infection or contact sensitization.