Rotavirus-specific intestinal resident memory T cells induced by oral vaccination in early-life mice may contribute to protective immunity.

Resident memory T cells (Trm) are key mediators of protective immunity at barrier sites, yet their development during early life remains poorly defined. Here, we show that early-life oral vaccination with a heterologous rhesus rotavirus (RV) induces short-lived intestinal Trm that are negative by intravascular staining and express a CD44+CD69+CD103+/-P2X7R+ phenotype. Blocking lymphocyte homing with an anti-α4β7 antibody during vaccination did not alter the magnitude of RV-specific intestinal T cells or affect protection following murine RV challenge. In contrast, reduction of RV-specific intraepithelial lymphocytes by nicotinamide adenine dinucleotide treatment, or genetic deletion of the aryl hydrocarbon receptor repressor (Ahrr-/- mice)-which also exhibit decreased intraepithelial CD8+ T cells after infection-resulted in increased viral antigen shedding upon challenge. These results suggest that intestinal Trm cells induced by early-life vaccination may contribute to protection against RV infection.