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Cell. 2015 Sep 10;162(6):1322-37. doi: 10.1016/j.cell.2015.08.004. Epub 2015 Aug 18.

Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions.

Author information

1
Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany.
2
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3
Institute of Pathology, Charité University Hospital Berlin, 10117 Berlin, Germany.
4
Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
5
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rgermain@nih.gov.
6
Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany. Electronic address: wkastenm@uni-bonn.de.

Abstract

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.

PMID:
26296422
PMCID:
PMC4567961
DOI:
10.1016/j.cell.2015.08.004
[Indexed for MEDLINE]
Free PMC Article

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