Glennie Nelson D, Volk Susan W, Scott Phillip
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2017 Apr 18;13(4):e1006349. doi: 10.1371/journal.ppat.1006349. eCollection 2017 Apr.
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细胞对于建立针对多种不同病原体的保护性免疫是必需的，尽管介导CD4⁺驻留记忆T细胞发挥保护作用的机制仍在研究中。在本研究中，我们利用利什曼原虫主要感染后产生的一群具有保护性的皮肤驻留、产生IFNγ的CD4⁺记忆T细胞来解决这个问题。我们之前发现驻留记忆T细胞招募循环效应T细胞以增强免疫力。在此我们表明，驻留记忆CD4⁺T细胞介导免疫小鼠中观察到的迟发型超敏反应，并且在没有循环T细胞的情况下提供保护。这种保护在攻击后迅速发生，并且需要招募和激活炎性单核细胞，这些细胞通过产生活性氧和一氧化氮来限制寄生虫。总体而言，这些数据突出了组织驻留记忆细胞在招募和激活炎性单核细胞方面的新作用，并强调了皮肤驻留T细胞在皮肤利什曼病免疫中所起的核心作用。
