Tissue-resident memory T (TRM) cells are uniquely positioned to provide an initial line of defense against invading microorganisms; airway-resident memory CD8 T (TARM) cells have been shown to confer protective immunity against a number of respiratory pathogens, including influenza virus and M. tuberculosis. Unlike TRM at other anatomical sites, TARM are not maintained via cytokine-driven homeostatic proliferation in the airways but must be continuously recruited from the circulation. We show that there exists a defect in TARM cell recruitment in mice infected with influenza virus via either intramuscular or intraperitoneal route as compared to the intranasal route. However, the mechanism(s) that enable intranasally-primed memory T cells to preferentially migrate to the airways have not been identified. Based on our preliminary data, we hypothesize that the candidate chemokine receptor, CXCR6, is responsible for steady-state trafficking of influenza-specific TARM cells to the airways from the general circulation. Our results show that CD8 T cell recruitment to the lung airways is significantly restricted in CXCR6 KO mice as compared to WT, while CD8 T cell numbers in the spleen remain constant. This study could help advance the field of cell-mediated vaccines to promote pathogen-specific T cell recruitment to the lung airways, enhancing protective immunity to respiratory pathogens.
- Copyright © 2013 by The American Association of Immunologists, Inc.