Distinctive CD8+ T cell activation by antigen-presenting plasmacytoid dendritic cells compared to conventional dendritic cells
Plasmacytoid dendritic cells (pDCs) play a pivotal role in immune responses, particularly against viral infections. pDCs exhibit diverse functions, including interferon production, cytokine secretion, and antigen presentation. Here, we investigate the antigen cross-presentation capacity of pDCs and their role in CD8<sup>+</sup> T cell activation. Utilizing a culturing system with CD8<sup>+</sup> T cells and autologous pDCs derived from circulating CD34<sup>+</sup> hematopoietic stem and progenitor cells, we demonstrate that pDCs efficiently activate CD8<sup>+</sup> T cells via cross-presentation, promoting T cell expansion and cytotoxic activity. The antigen presentation capacity of pDCs is comparable to that of monocyte-derived dendritic cells (moDCs) and myeloid dendritic cells, which are known for their efficient antigen-presentation capacity. Transcriptomic analysis reveals genetic signatures in CD8<sup>+</sup> T cells activated by pDCs distinct from moDCs, suggesting different activation mechanisms. These findings underscore the importance of pDCs in antigen presentation and their contribution to CD8<sup>+</sup> T cell activation.
Authors
- Lasse S. Kristensen (ORCID: https://orcid.org/0000-0002-5980-7939)
- Ulrich Kalinke (ORCID: https://orcid.org/0000-0003-0503-9564)
- Albert Gris‐Oliver (ORCID: https://orcid.org/0000-0003-1802-9541)
- Renée Marije van der Sluis (ORCID: https://orcid.org/0000-0002-7668-2517)
- Anders Laustsen (ORCID: https://orcid.org/0000-0002-0306-1736)
- Rasmus Otkjær Bak (ORCID: https://orcid.org/0000-0002-7383-0297)
- Bibiana Costa
- Ian Helstrup Nielsen (ORCID: https://orcid.org/0009-0003-8736-9838)
- Trine Hyrup Mogensen (ORCID: https://orcid.org/0000-0002-1853-9704)
- M. Zeeshan Chaudhry (ORCID: https://orcid.org/0000-0002-1372-4257)
- Martin R. Jakobsen (ORCID: https://orcid.org/0000-0001-8847-9201)
- Marvin Werner (ORCID: https://orcid.org/0000-0003-1200-807X)
- Juan L. García‐Rodríguez (ORCID: https://orcid.org/0000-0002-1818-1781)
- Luka Čičin‐Šain (ORCID: https://orcid.org/0000-0003-3978-778X)
- Stephan Becker (ORCID: https://orcid.org/0000-0002-0122-3922)
- Kristine Raaby Gammelgaard
- Jesper G Pedersen
Institutions
- Aarhus University (DK)
- Aarhus University Hospital (DK)
- Medizinische Hochschule Hannover (DE)
- Helmholtz Centre for Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115413
- Citations
- 3
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Lundbeckfonden
- Danmarks Frie Forskningsfond
- Danmarks Frie Forskningsfond
- HORIZON EUROPE European Research Council