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

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.