Runx2 activity in CD8+ T cells promotes longevity and function during acute and chronic infection 4744

Abstract Description Runx family transcription factors (Runx1, Runx2, and Runx3) play important roles in the development and function of T cells. Our lab previously found that Runx2 is dispensable for the CD8+ T cell effector response to acute Lymphocytic Choriomeningitis Virus (LCMV), but is required for the longevity of the memory population. However, the mechanism by which it imparts this longevity is not described. To investigate the specific molecular functions of Runx2, we utilize retroviral overexpression and CRISPR knockout of Runx proteins in both ovalbumin-specific and LCMV-specific CD8+ T cells. Adoptive transfer of OT-1 or P14 cells with altered Runx protein expression followed by ovalbumin-expressing Listeria monocytogenes (LmOva) or LCMV infection (respectively) indicates that Runx2 is required for the expression of proteins associated with function and survival. Runx2 perturbation also alters the expression of Runx3, suggesting it may negatively regulate its expression. Further, Runx2-deficient T cells are unable to survive and are functionally impaired in the context of chronic LCMV infection. Preliminary analyses of both Runx binding sites and histone modifications in cells with perturbed Runx expression suggest that Runx2 and Runx3 may bind the same genomic sites and drive different epigenetic profiles. We propose that Runx2 establishes a genetic program in T cells that promotes both self-renewal and cytotoxicity, allowing for longevity and enduring function. Funding Sources T32 AI007405 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)