T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells

Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of “dirty” mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8⁺ T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared some transcriptional and phenotypic signatures associated with nonlymphoid Trm cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells and suggest vaccination strategies by which memory CD8⁺ T cell immunosurveillance can be regionalized to specific lymph nodes. Resident memory T (Trm) cells park within tissues without recirculating. Beura et al. demonstrate that Trm cells in lymph nodes derive from cells that emigrate from nonlymphoid tissues. Local booster immunization or reinfection at barrier tissues generated secondary lymph node memory T cells that were biased specifically toward draining lymph nodes where they were resident.