CD8 T cells require intrinsic GITR signaling for their clonal expansion during influenza infection in vivo (50.21)
The Journal of Immunology(2010)
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.
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