[PDF][PDF] Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions

S Eickhoff, A Brewitz, MY Gerner, F Klauschen… - Cell, 2015 - cell.com
S Eickhoff, A Brewitz, MY Gerner, F Klauschen, K Komander, H Hemmi, N Garbi, T Kaisho…
Cell, 2015cell.com
Host defense against viruses and intracellular parasites depends on effector CD8+ T cells,
whose optimal clonal expansion, differentiation, and memory properties require signals from
CD4+ T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation
of the two T cell types and their co-operation. Surprisingly, initial priming of CD4+ and CD8+
T cells was spatially segregated within the lymph node and occurred on different DCs with
temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs …
Summary
Host defense against viruses and intracellular parasites depends on effector CD8+ T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4+ T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4+ and CD8+ T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1+ DCs are the critical platform involved in CD4+ T cell augmentation of CD8+ T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology, as well as for translational application to the development of vaccines that evoke optimal T cell immunity.
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