Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses

Although tissue-resident memory T cells (TRM cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin TRM cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary TRM cells formed from pre-existing TRM cells, as well as from precursors recruited from the circulation. Newly recruited antigen-specific or bystander TRM cells were generated in the skin without displacement of the pre-existing TRM cell pool. Thus, pre-existing skin TRM cell populations are not displaced after subsequent infections, which enables multiple TRM cell specificities to be stably maintained within the tissue.S.L.P. was supported by the University of Melbourne (Elizabeth and Vernon Puzey Postgraduate Scholarship). T.G. was supported by a fellowship from the Sylvia and Charles Viertel Charitable Foundation. This work was supported by the National Health and Medical Research Council of Australia (to S.N.M. and L.K.M.) and the Australian Research Council (to S.N.M.)