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

Resident memory T cells (T(RM)) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While T(RM) 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(RM) using a model of skin infection with restricted antigen distribution. We find exquisite localization of LN T(RM) to the draining LN of infected skin. LN T(RM) 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(RM) in draining LNs, a process reinforced by antigen encounter in skin. Importantly, we demonstrate that LN T(RM) 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.