The pathogen recognition theory dictates that, upon viral infection, the innate immune system first detects microbial products and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that tissue resident memory CD8 T cells (TRMcells), non-recirculating cells located at common sites of infection, can achieve near-sterilizing immunity against viral infections by reversing this flow of information. Upon antigen resensitization within the mouse female reproductive mucosae, CD8+TRMcells secrete cytokines that trigger rapid adaptive and innate immune responses, including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near-sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8+TRMcells rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens.
Extrinsic Acquisition of CD80 by Antigen-Specific CD8+ T Cells Regulates Their Recall Immune Responses to Acute Viral Infection