%0 Journal Article %T Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes. %A Heim TA %A Schultz AC %A Delclaux I %A Cristaldi V %A Churchill MJ %A Ventre KS %A Lund AW %J Sci Immunol %V 9 %N 96 %D 2024 Jun 7 %M 38848340 %F 30.63 %R 10.1126/sciimmunol.adk8141 %X Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (TRMs) play an important role in site-specific immune memory, yet how LN TRMs 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 TRMs using a model of vaccinia virus-induced skin infection. LN TRMs 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 TRMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN TRMs 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.