Intestinal helminth infection induces highly functional resident memory CD4+ T cells in mice
Intestinal helminth infection induces highly functional resident memory CD4+ T cells in mice
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DOI：
10.1002/eji.201646575
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发表时间：
2017-02
影响因子：
5.4
通讯作者：
S. Steinfelder;S. Rausch;Dörte Michael;A. Kühl;S. Hartmann
中科院分区：
文献类型：
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作者：
S. Steinfelder;S. Rausch;Dörte Michael;A. Kühl;S. Hartmann
对肠道线虫的免疫需要CD 4 + Th 2细胞应答，包括IL-4和IL-13的产生。肠道线虫的慢性感染导致这些反应的下调，并且在慢性期或感染消除后在次级淋巴器官中检测到很少的功能性T辅助细胞（Th）2细胞。在这里，我们表明，与一个自然的鼠感染Heligmosomoides polygyrus，高功能的记忆Th 2细胞持续存在于固有层，此外在腹腔（PC）废除感染后。虽然两种组织驻留记忆（TRM）细胞群在TCR依赖性刺激时原位增殖并表达IL-4、IL-5和IL-13，但只有腹膜记忆细胞在用IL-33和IL-7进行TCR非依赖性刺激时表达高水平的IL-33受体并产生IL-5和IL-13。最重要的是，PC衍生的TRM细胞能够通过在转移到受体小鼠后降低雌性蠕虫的繁殖力来介导抗蠕虫作用。这些结果表明，nonlymphatic隔室可以作为水库的Th 2记忆细胞，而且，先天效应功能的Th 2记忆细胞仅限于CD 4+记忆T细胞驻留在PC。
Immunity to intestinal nematodes requires CD4⁺ Th2‐cell responses, including IL‐4 and IL‐13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection. While both tissue‐resident memory (TRM) populations proliferate in situ and express IL‐4, IL‐5, and IL‐13 upon TCR‐dependent stimulation, only peritoneal memory cells express high levels of the IL‐33 receptor and produce IL‐5 and IL‐13 upon TCR‐independent stimulation with IL‐33 and IL‐7. Most importantly, PC‐derived TRM cells are able to mediate anti‐helminthic effects by decreasing the fecundity of female worms upon transfer into recipient mice. These results show that nonlymphoid compartments can serve as reservoirs for Th2 memory cells, and furthermore that innate effector function of Th2 memory cells is restricted to CD4⁺ memory T cells residing in the PC.