Robust Anti-Viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions
Open accessAbstract
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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XCR1+ cDCs can present antigen on both class I and class II MHC molecules, serving as a platform for simultaneous interactions between CD4+ and CD8+ T cells.
“XCR1+ cDCs are able to present antigen on both class I and II MHC molecules, serving as a platform for simultaneous interactions between CD4+ and CD8+ T cell (41).”
From Effect of CpG Depletion of Vector Genome on CD8+ T Cell Responses in AAV Gene Therapy (2021) · cites this paper as [41]
Cooperation between pDCs and cDCs in priming of anti-viral CD8+ T cells is not unique to AAV, as documented for responses to vaccinia virus.
“Cooperation between pDCs and cDCs in priming of anti-viral CD8+ T cells is not unique to AAV, as has been documented in detail for responses to vaccinia virus.27”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [27]
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“XCR1 cDCs are able to present antigen on both class I and II MHC molecules, serving as a platform for simultaneous interactions between CD4 and CD8 T cell (41).”
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- Authors
- Eickhoff, S., Brewitz, A., Gerner, M. Y., Klauschen, F., Komander, K., Hemmi, H., Garbi, N., Kaisho, T., Germain, R. N., & Kastenmüller, W.
- Affiliations
- University of Bonn (DE)
- National Institutes of Health (US)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- RIKEN Center for Integrative Medical Sciences (JP)
- Corresponding author
- Germain, Ronald Nathan
- Kastenmüller, Wolfgang
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 162
- Issue
- 6
- Pages
- 1322-1337
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4567961
- OpenAlex
- W1564678055
- Cited by
- 337
- References
- 49
- Citations by year
- 2026: 12 · 2025: 28 · 2024: 19 · 2023: 42 · 2022: 28 · 2021: 43 · 2020: 33 · 2019: 30 · 2018: 37 · 2017: 32 · 2016: 30 · 2015: 3
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Japan Society for the Promotion of Science (26293106)
- National Institute of Allergy and Infectious Diseases (Z01AI000545, K22AI108628)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- antiviral immunity, dendritic cell subsets, CD8+ T cell priming, CD4+ T cell help, dendritic cell-T cell interaction, XCR1+ dendritic cells, MHC class I antigen presentation, MHC class II antigen presentation, lymph nodes, clonal expansion, memory T cells, vaccine design
- MeSH terms
- Animals, Antigens, Viral, Cell Communication, Dendritic Cells, Lymph Nodes, Spleen, Vaccinia, Vaccinia virus, CD4-Positive T-Lymphocytes, Antigen Presentation, CD8-Positive T-Lymphocytes, Receptors, Chemokine, Mice
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