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

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.