Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity.
Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity.
复制标题
DOI：
10.1038/nature10851
复制
发表时间：
2012-02-29
期刊：
影响因子：
64.8
通讯作者：
Kupper, Thomas S.
中科院分区：
文献类型：
--
作者：
Jiang, Xiaodong;Clark, Rachael A.;Liu, Luzheng;Wagers, Amy J.;Fuhlbrigge, Robert C.;Kupper, Thomas S.
保护性T细胞记忆一直被认为存在于血液和淋巴结中，但最近提出了由驻留记忆T（TRM）细胞介导的外周组织免疫记忆的概念。在这里，我们在小鼠中显示，局部牛痘病毒（VACV）皮肤感染产生长寿命的非再循环的CD 8+皮肤TRM细胞，驻留在整个皮肤内。这些皮肤TRM细胞是有效的效应细胞，并且在提供针对皮肤再感染的快速长期保护方面上级循环中央记忆T（TCM）细胞。我们发现，急性VACV感染后，CD 8 +T细胞迅速募集到皮肤。CD 8 + T细胞向皮肤的募集不依赖于CD 4 +T细胞和干扰素-γ，但需要CD 8 +T细胞表达E-和P-选择素配体。使用联体小鼠，我们进一步表明，循环的CD 8 + TCM和CD 8+皮肤TRM细胞都是在皮肤感染后产生的;然而，CD 8 + TCM细胞在血液和淋巴结之间再循环，而TRM细胞保留在皮肤中。皮肤CD 8 + TRM细胞产生效应细胞因子，并在感染后持续至少6个月。具有CD 8+皮肤TRM细胞的小鼠迅速清除随后的VACV再感染，而具有循环TCM但没有皮肤TRM细胞的小鼠显示出极大受损的病毒清除，表明TRM细胞提供了上级保护。最后，我们表明，由于局部VACV皮肤感染产生的TRM细胞不仅存在于感染部位，而且还分布在整个皮肤表面，并持续数月。反复的再感染导致高度保护性的TRM细胞在非受累皮肤中进行性积累。这些发现对我们理解上皮与环境界面的保护性免疫记忆具有重要意义，并为疫苗提供了新的策略，以保护免受组织嗜性生物的侵害。
Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (TRM) cells has been proposed,,,,. Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8+skin TRMcells that reside within the entire skin. These skin TRMcells are potent effector cells, and are superior to circulating central memory T (TCM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8+T cells are rapidly recruited to skin after acute VACV infection. CD8+T-cell recruitment to skin is independent of CD4+T cells and interferon-γ, but requires the expression of E- and P-selectin ligands by CD8+T cells. Using parabiotic mice, we further show that circulating CD8+TCMand CD8+skin TRMcells are both generated after skin infection; however, CD8+TCMcells recirculate between blood and lymph nodes whereas TRMcells remain in the skin. Cutaneous CD8+TRMcells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8+skin TRMcells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating TCMbut no skin TRMcells showed greatly impaired viral clearance, indicating that TRMcells provide superior protection. Finally, we show that TRMcells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective TRMcells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.
登录
查看更多内容
影响因子：
82.9
作者：
Conrad, Curdin;Boyman, Onur;Nestle, Frank O.
通讯作者：
Nestle, Frank O.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
32.4
作者：
Liu, Luzheng;Fuhlbrigge, Robert C.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
17.1
作者：
Clark RA;Watanabe R;Teague JE;Schlapbach C;Tawa MC;Adams N;Dorosario AA;Chaney KS;Cutler CS;Leboeuf NR;Carter JB;Fisher DC;Kupper TS
通讯作者：
Kupper TS
DOI：
10.1073/pnas.0912943107
发表时间：
2010-04-20
影响因子：
11.1
作者：
Jiang, Xiaodong;Campbell, James J.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.