Sowell Ryan T, Goldufsky Josef W, Rogozinska Magdalena, Quiles Zurisaday, Cao Yanxia, Castillo Eliseo F, Finnegan Alison, Marzo Amanda L
Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612.
Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612; and.
J Immunol. 2017 Oct 1;199(7):2536-2546. doi: 10.4049/jimmunol.1501638. Epub 2017 Aug 16.
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1. Last, we show that IL-15 complexes delivered locally to mucosal tissues without reinfection is an effective strategy to enhance establishment of tissue resident memory CD8 T cells within mucosal tissues. This study provides mechanistic insight into how IL-15 controls the generation of memory CD8 T cells and influences their trafficking and ability to take up residence within peripheral tissues.
白细胞介素-15(IL-15)是一种重要的细胞因子,已知其可促进T细胞存活并激活记忆表型CD8 T细胞的效应功能。阻断IL-15信号也会显著影响组织特异性效应和记忆CD8 T细胞的形成。在本研究中,我们证明IL-15通过首先促进记忆CD8 T细胞积聚到黏膜组织中,其次通过维持Bcl-6和T-bet的表达来影响其生成。我们表明,这种募集机制在很大程度上依赖于雷帕霉素靶蛋白及其随后对FoxO1的失活作用。最后,我们表明,在无再次感染的情况下局部递送至黏膜组织的IL-15复合物是增强黏膜组织内组织驻留记忆CD8 T细胞建立的有效策略。本研究为IL-15如何控制记忆CD8 T细胞的生成以及影响其在外周组织中的迁移和驻留能力提供了机制上的见解。