A temporal role of type I interferon signaling in CD8 + T cell maturation during acute West Nile virus infection

A genetic absence of the common ifn- α/β signaling receptor (ifnar) in mice is associated with enhanced viral replication and altered adaptive immune responses. however,analysis of ifnar -/- mice is limited for studying the functions of type i ifn at discrete stages of viral infection. to define the temporal functions of type i ifn signaling in the context of infection by west nile virus (wnv),we treated mice with mar1-5a3,a neutralizing,non cell-depleting anti-ifnar antibody. inhibition of type i ifn signaling at or before day 2 after infection was associated with markedly enhanced viral burden,whereas treatment at day 4 had substantially less effect on wnv dissemination. while antibody treatment prior to infection resulted in massive expansion of virus-specific cd8 + t cells,blockade of type i ifn signaling starting at day 4 induced dysfunctional cd8 + t cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. thus,only the later maturation phase of anti-wnv cd8 + t cell development requires type i ifn signaling. wnv infection experiments in batf3 -/- mice,which lack cd8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation,revealed a similar effect of blocking ifn signaling on cd8 + t cell maturation. collectively,our results suggest that cell non-autonomous type i ifn signaling shapes maturation of antiviral cd8 + t cell response at a stage distinct from the initial priming event. © 2011 pinto et al.