CD8 T cells require intrinsic GITR signaling for their clonal expansion during influenza infection in vivo (50.21)

Abstract

Abstract Several members of the tumor necrosis factor receptor family regulate T cell expansion by influencing T cell activation and survival. Among these, glucocorticoid-induced TNF receptor family-related gene (GITR) is of interest, as it is expressed on both effector and regulatory T cells. While much work has focused on the role of GITR on regulatory T cells, little is known about its role on effector T cells in an infectious disease context. We sought, therefore, to examine the intrinsic role of GITR on CD8 T cells during a viral infection. To do this, we employed an adoptive transfer model where WT and GITR-/- TCR transgenic OT-I CD8 T cells were forced to compete with each other in response to infection with a recombinant influenza virus carrying the ovalbumin epitope recognized by OT-I, Influenza A/X31-OVA. In both the primary and secondary response to virus profound defects in GITR-/- OT-I T cell numbers were detected in all organs examined. Further investigation revealed that the decreased number of GITR-/- OT-I T cells was not due to a homing or proliferative defect, but rather that GITR was important for TRAF2 and TRAF5 mediated T cell survival signaling. Moreover, we also used a similar adoptive transfer model to show that GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR antibody. These results highlight the importance of GITR as a CD8 T cell costimulator during acute viral infection.