Augmented TCR-mediated signaling in infant T cells enables robust responses to respiratory virus infection

Abstract Infants require coordinated immune responses to prevent succumbing to multiple infectious challenges, particularly in the respiratory tract. The mechanisms by which infant T cells are functionally adapted for these responses are not well understood. Here, we demonstrate using an in vivo co-transfer model that infant T cells generate greater numbers of lung-homing effector cells to influenza infection compared to adult T cells in the same host, due to augmented TCF-1 downregulation and T cell receptor (TCR)-mediated signaling. Importantly, infant T cells show increased sensitivity to low antigen doses, originating at the interface between T cells and antigen-bearing accessory cells–through actin-mediated mobilization of signaling molecules to the immune synapse. This enhanced signaling was also observed in human infant versus adult T cells. Our findings provide a mechanism for how infants control pathogen load and dissemination, important for designing developmentally-appropriate strategies for promoting immune responses at this vulnerable life stage.