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

Although tissue-resident memory T cells (T RM cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin T RM 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 T RM cells formed from pre-existing T RM cells, as well as from precursors recruited from the circulation. Newly recruited antigen-specific or bystander T RM cells were generated in the skin without displacement of the pre-existing T RM cell pool. Thus, pre-existing skin T RM cell populations are not displaced after subsequent infections, which enables multiple T RM cell specificities to be stably maintained within the tissue. Mackay, Mueller and colleagues show that tissue-resident memory T cells proliferate in situ in response to local antigen and persist during subsequent antigen encounters.