CD8+ T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8+ T cells that persist at front-line sites of microbial exposure: to serve 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 mouse reproductive tract encountered cognate antigen, they expressed interferon-γ (IFN-γ), potentiated robust local expression of inflammatory chemokines and induced rapid recruitment of circulating memory CD8+ T cells. Anamnestic responses in front-line tissues are thus an integrated collaboration between front-line and circulating populations of memory CD8+ T cells, and vaccines should establish both populations to maximize rapid responses.
Bibliographical noteFunding Information:
We thank M. Mescher (University of Minnesota) for IFN-γ-deficient OT-I mice, and S. Jameson for discussions. Supported by the US National Institutes of Health (R01AI084913-01 to D.M., DP2OD006467 (by the Office of The Director) to D.M., and T32AI007313 to J.M.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.