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

Abstract

AbstractResident memory T cells (TRM) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While TRMare 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 TRMusing a model of skin infection with restricted antigen distribution. We find exquisite localization of LN TRMto the draining LN of infected skin. LN TRMformation 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 TRMin draining LNs, a process reinforced by antigen encounter in skin. Importantly, we demonstrate that LN TRMare 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.One Sentence SummaryT cell egress out of virally infected skin via afferent lymphatic vessels seeds CD8+resident memory T cells in the draining lymph node.