Dendritic cells undergo maturation following respiratory vaccinia virus infection

Abstract

Previous in vitro studies have shown that dendritic cells (DC) fail to undergo maturation following vaccinia virus (VV) infection. In spite of this finding, in vivo studies suggest a role for direct presentation of viral antigen in the generation of a virus‐specific CD8+ T cell response. These seemingly contradictory findings raise the question of how DC maturation is regulated in vivo. Using a model of respiratory VV infection, we find that infected DC are capable of up‐regulating expression of both CD80 and CD86. Thus in contrast to what has been suggested by in vitro studies, in vivo, VV infected, mature DC are candidates for T cell activation. Infected DC exhibiting a mature phenotype are present in both CD8+ and CD8− DC populations, suggesting both subsets can contribute to T cell activation. In addition, a subpopulation of non‐infected DC, both CD8+ and CD8−, are triggered to undergo maturation. Certainly the CD8+ DC are potential contributors to activation via cross‐presentation of antigen. Results from initial studies of naïve T cell activation by non‐infected CD8+ DC support this interpretation. These data provide the first analysis of VV infection of defined DC subsets in vivo following respiratory infection and the subsequent effect on their maturation and activating potential, as well as novel insights into our understanding of the generation of the adaptive immune response.