Cell. 2015 Sep 10.
Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions.
Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K, Hemmi H, Garbi N, Kaisho T, Germain RN, Kastenmüller W.
- •Initial activation of CD4+ and CD8+ T lymphocytes is spatially separated
- •Later during infection, XCR1+ DCs present antigen to both lymphocyte subsets
- •XCR1+ DCs are a critical platform for delivery of CD4+ T cell help to CTL
- •Absence of XCR1+ DCs leads to aberrant memory CD8+ T cell differentiation
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.