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

作者：Gurevich Irina^*; Feferman Tali; Milo Idan; Tal Orna; Golani Ofra; Drexler Ingo; Shakhar Guy^*

来源：European Journal of Immunology, 2017, 47(10): 1802-1818.

DOI：10.1002/eji.201747042

• Antigen presentation
• CD8(+) T cells
• Cell migration
• Dendritic cells
• In vivo imaging
• T-cell activation
• Vaccinia virus

Antigen (Ag) specific activation of naive T cells 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(+) 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 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(+) T cells by increasing the number of effective presenting cells and salvaged T-cell priming when Ag-donor DCs could not present Ag.

• 出版日期2017-10