Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes

Abstract

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T_RMs) play an important role in site-specific immune memory, yet how LN T_RMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8⁺ T cells as they seeded skin and LN T_RMs using a model of vaccinia virus–induced skin infection. LN T_RMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8⁺ T cells from the skin, already poised for residence. Effector CD8⁺ T cell transit through skin was required to populate LN T_RMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T_RMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8⁺ T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.