CD4+ FoxP3+ regulatory T cells control effector T cell responses to murine cytomegalovirus (VIR10P.1169)

Human cytomegalovirus causes a persistent, lifelong infection. The virus persists in a latent state and undergoes intermittent subclinical viral reactivation. Such reactivation drives the accumulation of “inflationary” T cells that suppress viral replication. While T cells are critical to maintain control of infection, the factors that prevent T cells from driving complete viral elimination remain unclear. Here, we investigated the role of regulatory T cells (Treg) in a mouse model of persistent CMV infection using FoxP3-diphtheria toxin receptor (DTR) mice. FoxP3-DTR mice were infected with murine CMV (MCMV) and then Treg were depleted via administration of DT several months later. Treg depletion resulted in a dramatic increase in the numbers of MCMV-specific CD4 and CD8 T cells in the spleen which functionally, produced significantly higher levels of IFN-γ and IL-2. Strikingly, Treg depletion led to a significant decrease in splenic viral load. We are initiating experiments using a spleen viral reactivation assay, to determine the effect of Treg depletion on latent virus. Combined, these data suggest that Treg promote persistent MCMV infection, in part, by suppressing T cell activation.