The role of Runx2 in CD8+ T cell memory during acute LCMV Armstrong infection

Abstract

Abstract During an acute viral infection, CD8+ T lymphocytes with T cell receptors (TCRs) specific for pathogen epitopes undergo clonal expansion and clear viral infection. After infection is cleared, the majority of the pathogen-specific CD8+ T cells undergo apoptosis, leaving a small population of memory CD8+ T cells that rapidly proliferate upon reinfection of the same antigen. How differentiation between the terminal effector cell population (TECs) and the memory cell population (MPECs) is regulated is not completely understood. Our research has focused on the role of the runt-related transcription factor Runx2 in CD8+ T cell memory formation during acute LCMV Armstrong infection. We have found using a mouse line with a T cell-specific deletion of Runx2 that loss of Runx2 leads to a defect in the formation of MPECs. We have also found that this defect is intrinsic to virus-specific CD8+ T cells. To further elucidate the upstream signaling pathways regulating Runx2 we have examined TCR signaling, cytokine signaling, and transcription factor regulation. These studies indicate that IRF4 levels inversely correlate with Runx2 expression in in vitro culture systems. We have also examined downstream pathways regulated by Runx2 in T cells, including gene expression and migration. This analysis has not revealed Runx2-dependent changes in gene expression in T cells isolated from LCMV-infected mice at D6 post-infection, nor in T cells stimulated in vitro; furthermore, we do not observe altered homing properties of Runx2-deficient T cells. Current studies are focused on examining Runx2 phosphorylation during memory CD8+ T cell differentiation. Overall, our data indicate an important role for Runx2 in CD8+ T cell memory during LCMV Armstrong infection.