Depleting CD103(+) resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa

The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8(+) CD103(+) resident memory T cells (T(RM)), which locally survey tissues without recirculating. Oral antigen re-encounter during the effector phase of immune responses potentiated T(RM) establishment within tongue, gums, palate, and cheek. Upon reactivation, oral T(RM) triggered changes in somatosensory and innate immune gene expression. We developed in vivo methods for depleting CD103(+) T(RM) while sparing CD103(neg) T(RM) and recirculating cells. This revealed that CD103(+) T(RM) were responsible for inducing local gene expression changes. Oral T(RM) putatively protected against local viral infection. This study provides methods for generating, assessing, and in vivo depleting oral T(RM), documents their distribution throughout the oral mucosa, and provides evidence that T(RM) confer protection and trigger responses in oral physiology and innate immunity.