Sensing and alarm function of resident memory CD8(+) T cells

CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and antiviral cytokine secretion. Here, we identify an additional function for memory CD8(+) T cells persisting at frontline sites of microbial exposure: as local sensors of previously encountered antigens that precipitate innate-like alarm signals and draw circulating memory CD8(+) T cells into the tissue. When memory CD8(+) T cells residing in the female reproductive tract encountered cognate antigen, they expressed interferon-γ (IFN-γ), potentiated robust local inflammatory chemokine expression and induced rapid recruitment of circulating memory CD8(+) T cells. Anamnestic responses in frontline tissues are thus an integrated collaboration between frontline and circulating populations of memory CD8(+) T cells, and vaccines should establish both populations to maximize rapid responses.