Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis.

组织驻留记忆T细胞（tissue-resident memory T cells）是建立针对多种不同病原体的保护性免疫所必需的，尽管CD4+组织驻留记忆T细胞介导保护性免疫的具体机制仍有待明确。本研究针对杜氏利什曼原虫（Leishmania major）感染后诱导生成的、具备保护性的皮肤驻留型γ干扰素（IFNγ）分泌性CD4+记忆T细胞群体，对这一问题展开了探究。我们此前的研究表明，组织驻留记忆T细胞可招募循环效应T细胞以增强免疫应答。本研究证实，组织驻留记忆CD4+ T细胞可介导免疫小鼠体内出现的迟发型超敏反应，并在无循环T细胞参与的情况下实现免疫保护。该保护作用在病原体攻毒后快速启动，且依赖于炎性单核细胞的招募与活化——这类细胞可通过产生活性氧与一氧化氮来抑制寄生虫增殖。综上，本研究数据揭示了组织驻留记忆细胞在招募并活化炎性单核细胞方面的全新功能，并凸显了皮肤驻留T细胞在皮肤利什曼病（cutaneous leishmaniasis）免疫防御中的核心作用。