Role of cell cycle regulator E2F1 in regulating CD8 T cell responses during acute and chronic viral infection*1

Abstract

To determine the role of cell cycle regulatory protein E2F1 in T cell immunity, we compared antigen-specific CD8 T cell responses between wild type (+/+) and E2F1-deficient (E2F1−/−) mice following an acute and chronic infection with lymphocytic choriomeningitis virus (LCMV). During an acute LCMV infection, although LCMV-specific effector CD8 T cells from E2F1−/− mice were less susceptible to activation-induced cell death (AICD) in vitro, E2F1 deficiency had no significant effect on the: (1) expansion or contraction of virus-specific CD8 T cell responses; (2) proliferative renewal of memory CD8 T cells in both lymphoid and non-lymphoid organs. Importantly, under conditions of repeated antigenic stimulation in the setting of a chronic LCMV infection, E2F1 deficiency did not preclude the exhaustion of CD8 T cells specific to the immunodominant epitope nucleoprotein 396–404 (NP396–404). Taken together, our studies show that E2F1, an important tumor suppressor and cell cycle regulator, may not have a non-redundant role in regulating CD8 T cell responses in acute and chronic LCMV infections.