Targeted Expansion of Tissue-Resident CD8+ T Cells to Boost Cellular Immunity in the Skin
Targeted Expansion of Tissue-Resident CD8+ T Cells to Boost Cellular Immunity in the Skin
复制标题
DOI：
10.1016/j.celrep.2019.10.126
复制
发表时间：
2019-12-03
期刊：
影响因子：
8.8
通讯作者：
Nolz, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Hobbs, Samuel J.;Nolz, Jeffrey C.
组织驻留记忆(T-RM)CD8(+)T细胞定位于环境屏障组织内，以提供抵御病原体进入的第一道防线，但这些专门的T细胞群体是否可以容易地增强以提高保护性免疫力尚不清楚。在这里，我们证明了重复激活稀有的内源性T-RM CD8(+)T细胞，仅使用抗原肽局部应用会导致迟发性超敏反应，并使抗原特异性T-RM CD8(+)T细胞的数量增加约15倍，尤其是在受攻击的皮肤中。皮肤中扩大的T-RM CD8(+)T细胞来自于从循环中招募的记忆T细胞，这些T细胞在局部抗原相遇后成为CD69(+)组织的居民。值得注意的是，使用双肽挑战策略可以强迫具有不同抗原特异性的新的循环记忆CD8(+)T细胞成为组织驻留细胞。扩增的T-RM CD8(+)T细胞显著增强了抗病毒保护，表明这种方法可以用来快速提高组织特异性细胞免疫。
Tissue-resident memory (T-RM) CD8(+) T cells are positioned within environmental barrier tissues to provide a first line of defense against pathogen entry, but whether these specialized T cell populations can be readily boosted to increase protective immunity is ill defined. Here, we demonstrate that repeated activation of rare, endogenous T-RM CD8(+) T cells, using only topical application of antigenic peptide causes delayed-type hypersensitivity and increases the number of antigen-specific T-RM CD8(+) T cells, specifically in the challenged skin by similar to 15-fold. Expanded T-RM CD8(+) T cells in the skin are derived from memory T cells recruited out of the circulation that became CD69(+) tissue residents following a local antigen encounter. Notably, recruited circulating memory CD8(+) T cells of a different antigen specificity could be coerced to become tissue resident using a dual-peptide challenge strategy. Expanded T-RM CD8(+) T cells significantly increase anti-viral protection, suggesting that this approach could be used to rapidly boost tissue-specific cellular immunity.