Antiviral activity of Cytomegalovirus-specific CD4+ T cells against lytically infected non-haemopoietic cells

HCMV establishes a lifelong latent infection in its host, eliciting a broad immune response involving both the innate and adaptive arms of immunity. In immunocompromised individuals, recovery of the HCMV-specific CD4+ T cell response is associated with a lower risk of HCMV reactivation and disease, suggesting that CD4+ T cells contribute significantly to control of viral replication in vivo. However, most prior studies of the HCMV-specific CD4+ T cell response have been performed with the aim of either predicting those at risk for HCMV reactivation and end-organ disease, or identifying markers which are associated with higher risk of HCMV viraemia. Few studies have examined the mechanisms of viral control of CD4+ T cells in response to cells lytically infected with HCMV. In this paper, we show that CD4+ T cells from a HCMV-seropositive donor can prevent viral dissemination in autologous fibroblasts, that the secretome from these cells is also antiviral, and that IFN-γ is a key cytokine in the secretome. We also show that MHC Class II antigen presentation by monocytes was critical to driving this HCMV-specific CD4+ T cell response.