Spatial Analysis of CD8+ T cell Activation After Local Viral Replication in the Skin

Abstract

Abstract The generation of a robust CD8+ T cell response is critical for the elimination of virally infected cells and is dependent on presentation of viral antigen in the draining lymph node. Although we know much about antigen presentation in general, how antiviral T cell activation is precisely accomplished at the spatial level remains incompletely understood. Much of our knowledge of spatial details of viral antigen presentation derives from studies in which virus is subcutaneously injected, which likely differs greatly from presentation after virus replicates in the tissue and naturally drains to the regional lymph node. In order to better understand viral antigen presentation in the lymph node after viral replication in the skin and the impact on the initiation of CD8+ T cell responses, we infected mice in the ear pinna with vaccinia virus (VACV) epicutaneously using a bifurcated needle. VACV replicates to high titers in the skin, and viral antigen and genomes are detectable in the draining cervical lymph node by day 5 post infection, far beyond that after subcutaneous VACV injection. We are currently exploring the spatiotemporal dynamics of T cell activation as well as the antigen presenting cell subsets important for priming after epicutanous VACV infection. These findings are of significance for both our basic understanding of antiviral immunity and for the development of new T cell-based vaccination strategies, where optimization of CD8+ T cell responses is essential.