Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Dermatology, St. Luke's International Hospital, Tokyo, Japan.
Immunity. 2019 May 21;50(5):1249-1261.e5. doi: 10.1016/j.immuni.2019.03.002. Epub 2019 Apr 2.
Regulated activation of the cytokine TGF-β by integrins αβ and αβ expressed on keratinocytes is required for residence of epidermal-resident memory T cells, but whether skin-derived signals also affect recirculating memory cells in the skin remains unclear. Here, we show that after resolution of skin vaccinia virus (VV) infection, antigen-specific circulating memory CD8 T cells migrated into skin. In mice lacking αβ and αβ integrins (Itgb6Itgb8-K14-cre), the absence of epidermal-activated TGF-β resulted in a gradual loss of E- or P-selectin-binding central and peripheral memory populations, which were rescued when skin entry was inhibited. Skin recirculating memory cells were required for optimal host defense against skin VV infection. These data demonstrate that skin migration can persist after resolution of local skin infection and that the cytokine environment within this nonlymphoid tissue shapes the differentiation state and persistence of the central and peripheral memory-T-cell pool.
表皮角质细胞表达的整合素 αβ 和 αβ 对细胞因子 TGF-β 的调控激活，是表皮驻留记忆 T 细胞定居所必需的，但皮肤来源的信号是否也影响皮肤中的循环记忆细胞尚不清楚。在这里，我们发现，在皮肤痘苗病毒（VV）感染得到解决后，抗原特异性循环记忆 CD8 T 细胞迁移到皮肤中。在缺乏 αβ 和 αβ 整合素（Itgb6Itgb8-K14-cre）的小鼠中，表皮激活的 TGF-β 的缺失导致 E-或 P-选择素结合的中央和外周记忆群体逐渐丧失，当抑制皮肤进入时，这种缺失得到挽救。皮肤循环记忆细胞是宿主针对皮肤 VV 感染的最佳防御所必需的。这些数据表明，局部皮肤感染解决后，皮肤迁移仍可持续，并且这种非淋巴组织内的细胞因子环境决定了中央和外周记忆 T 细胞库的分化状态和持久性。
