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. In the oral mucosa, Stolley et al. characterize resident memory T cell (T-RM) distribution, ontogeny, role in protective immunity, and diverse functions, while describing strategies for locally augmenting or systemically depleting CD103(+) T-RM.

Automated summary

The oral mucosa is a frontline for microbial exposure and harbors CD8(+) CD103(+) resident memory T cells (T-RM) that locally survey tissues without recirculating. Oral antigen re-encounter enhances T-RM establishment and triggers changes in gene expression. These T-RM putatively protect against local viral infection.