Heim Taylor A, Schultz Austin C, Delclaux Ines, Cristaldi Vanessa, Churchill Madeline J, Lund Amanda W
Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, NY, USA.
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR.
bioRxiv. 2023 Aug 31:2023.08.29.555369. doi: 10.1101/2023.08.29.555369.
Resident memory T cells (T) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While T are also found in lymph nodes (LN), how they develop during primary infection and their functional significance remains largely unknown. Here, we track the anatomical distribution of anti-viral CD8 T cells as they simultaneously seed skin and LN T using a model of skin infection with restricted antigen distribution. We find exquisite localization of LN T to the draining LN of infected skin. LN T formation depends on lymphatic transport and specifically egress of effector CD8 T cells that appear poised for residence as early as 12 days post infection. Effector CD8 T cell transit through skin is necessary and sufficient to populate LN T in draining LNs, a process reinforced by antigen encounter in skin. Importantly, we demonstrate that LN T are sufficient to provide protection against pathogenic rechallenge. These data support a model whereby a subset of tissue infiltrating CD8 T cells egress during viral clearance, and establish regional protection in the draining lymphatic basin as a mechanism to prevent pathogen spread.
驻留记忆性T细胞（T细胞）在外周组织中为病原体和癌症提供快速、局部的保护。虽然在淋巴结（LN）中也发现了T细胞，但它们在初次感染期间如何发育及其功能意义在很大程度上仍不清楚。在这里，我们使用一种抗原分布受限的皮肤感染模型，追踪抗病毒CD8 T细胞在同时定植于皮肤和LN T时的解剖分布。我们发现LN T细胞精确地定位于感染皮肤的引流淋巴结。LN T细胞的形成依赖于淋巴转运，特别是效应性CD8 T细胞的流出，这些效应性CD8 T细胞在感染后12天就似乎准备好驻留。效应性CD8 T细胞通过皮肤的转运对于在引流淋巴结中填充LN T细胞是必要且充分的，这一过程因在皮肤中遇到抗原而得到加强。重要的是，我们证明LN T细胞足以提供针对致病性再次攻击的保护。这些数据支持了一个模型，即一部分组织浸润性CD8 T细胞在病毒清除期间流出，并在引流淋巴区域建立局部保护，作为防止病原体传播的一种机制。
