Intravital mucosal imaging of CD8⁺ resident memory T cells shows tissue-autonomous recall responses that amplify...

CD8⁺ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8⁺ resident memory T cells (T_RM cells) within the reproductive tracts of live female mice. We found that mucosal T_RM cells were highly motile, but paused and underwent in situ division after local antigen challenge. T_RM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent T_RM cell differentiation in situ. However, the proliferation of pre-existing T_RM cells dominated the local mucosal recall response and contributed most substantially to the boosted secondary T_RM cell population. We observed similar results in skin. Thus, T_RM cells can autonomously regulate the expansion of local immunosurveillance independently of central memory or proliferation in lymphoid tissue.