Type I IFN-Dependent T Cell Activation Is Mediated by IFN-Dependent Dendritic Cell OX40 Ligand Expression and Is Independent of T Cell IFNR Expression

Type I IFNs are important for direct control of viral infection and generation of adaptive immune responses. Recently, direct stimulation of CD4+ T cells via type I IFNR has been shown to be necessary for the formation of functional CD4+ T cell responses. In contrast, we find that CD4+ T cells do not require intrinsic type I IFN signals in response to combined TLR/anti-CD40 vaccination. Rather, the CD4 response is dependent on the expression of type I IFNR (IFNαR) on innate cells. Further, we find that dendritic cell (DC) expression of the TNF superfamily member OX40 ligand was dependent on type I IFN signaling in the DC, resulting in a reduced CD4+ T cell response that could be substantially rescued by an agonistic Ab to the receptor OX40. Taken together, we show that the IFNαR dependence of the CD4+ T cell response is accounted for exclusively by defects in DC activation.