Journal
CELL
Volume 162, Issue 6, Pages 1322-1337Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.08.004
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Funding
- NIAID
- NIH
- DFG Excellence Cluster ImmunoSensation in Bonn, Germany [SFB670/SFB704]
- NRW-Ruckkehrerprogramm of the German state of Northrhine-Westfalia
- Kishimoto Foundation
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science
- Human Frontier Science Program (HFSP) [RGY007/2011]
- Einstein Foundation Berlin
- Intramural Research Program
- Grants-in-Aid for Scientific Research [26293106] Funding Source: KAKEN
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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 antiviral 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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