Resident memory CD8 T cells trigger protective innate and adaptive immune responses

TLDR

The pathogen recognition theory posits that innate immunity first detects viral products and then instructs adaptive CD8 T cells. The study demonstrates that tissue‑resident memory CD8 T cells can achieve near‑sterilizing immunity by reversing the typical flow of information from innate to adaptive immunity. In the mouse female reproductive mucosa, antigen‑resensitized CD8(+) T(RM) cells secrete cytokines that rapidly activate adaptive and innate responses, including humoral immunity, dendritic cell maturation, and NK cell activation. The results show that CD8(+) T(RM) cells confer near‑sterilizing immunity to unrelated viral infections by rapidly triggering an antiviral state through amplified receptor‑derived signals.

Abstract

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 (T(RM) cells), 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(+) T(RM) cells 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(+) T(RM) cells rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens.