5 years ago

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

Orna Tal, Tali Feferman, Irina Gurevich, Guy Shakhar, Ofra Golani, Ingo Drexler, Idan Milo
Antigen (Ag)-specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their co-localization 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+ T cell-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 T cells 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+ T cells clustered, upregulated CD69, proliferated and differentiated into effectors. Few DCs sufficed for activation, and for efficient Ag dissemination 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+ T cells by increasing the number of effective presenting cells and salvaged T-cell priming when Ag-donor DCs could not present Ag. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747042

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