Active dissemination of cellular antigens by DCs facilitates CD8+ T-cell priming in lymph nodes.

Abstract

Antigen (Ag) specific activation of naïve Tcells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their colocalization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8+ Tcell-DC interactions to study the sites, routes, and cells mediating Ag transfer in mice. In vitro, Ag transfer from isolated ovalbumin (OVA)+ bone marrow (BM) DCs triggered widespread arrest, Ca2+ flux, and CD69 upregulation in OT-I Tcells contacting recipient DCs. Intravital two-photon imaging revealed that survival of Ag-donor DCs in LNs was required for Ag dissemination among resident CD11c+ DCs. Upon interaction with recipient DCs, CD8+ Tcells clustered, upregulated CD69, proliferated and differentiated into effectors. Few DCs sufficed for activation, and for efficient Ag dissemination lymphocyte function associated antigen 1 (LFA-1) expression on recipient DCs was essential. Similar findings characterized DCs infected with a replication-deficient OVA-expressing Vaccinia virus known to downregulate MHC-I. Overall, active Ag dissemination from live incoming DCs helped activate CD8+ Tcells by increasing the number of effective presenting cells and salvaged T-cell priming when Ag-donor DCs could not present Ag.