Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4 and CD8 T Cell Activation to Localized Viral Infection

Abstract

The dynamics of when and where CD4+ T cells provide help for CD8+ T cell priming and which dendritic cells (DCs) activate CD4+ T cells in vivo after localized infection are poorly understood. By using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node (LN) to concurrently visualize pathogen-specific CD4+ and CD8+ T cells, we found that early priming of CD4+ T cells involved clustering with migratory skin DCs. CD8+ T cells did not interact with migratory DCs and their activation was delayed, requiring later clustering interactions with LN-resident XCR1+ DCs. CD4+ T cells interacted with these late CD8+ T cell clusters on resid..