Distinctive CD8+ T cell activation by antigen-presenting plasmacytoid dendritic cells compared to conventional dendritic cells

Renée M van der Sluis; Juan L García-Rodríguez; Ian Helstrup Nielsen; Albert Gris-Oliver; Jennifer Becker; Bibiana Costa; M Zeeshan Chaudhry; Marvin Werner; Anders Laustsen; Jesper G Pedersen; Kristine R Gammelgaard; Trine H Mogensen; Ulrich Kalinke; Luka Cicin-Sain; Rasmus O Bak; Lasse S Kristensen; Martin R Jakobsen

doi:10.1016/j.celrep.2025.115413

Distinctive CD8⁺ T cell activation by antigen-presenting plasmacytoid dendritic cells compared to conventional dendritic cells

Cell Rep. 2025 Mar 11;44(3):115413. doi: 10.1016/j.celrep.2025.115413. Online ahead of print.

Authors

Renée M van der Sluis¹, Juan L García-Rodríguez², Ian Helstrup Nielsen², Albert Gris-Oliver², Jennifer Becker³, Bibiana Costa³, M Zeeshan Chaudhry⁴, Marvin Werner², Anders Laustsen², Jesper G Pedersen⁵, Kristine R Gammelgaard⁵, Trine H Mogensen⁶, Ulrich Kalinke⁷, Luka Cicin-Sain⁴, Rasmus O Bak⁸, Lasse S Kristensen², Martin R Jakobsen⁹

Affiliations

¹ Aarhus Institute of Advanced Studies, Aarhus University, 8000 Aarhus, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark. Electronic address: renee@biomed.au.dk.
² Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
³ Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
⁴ Department of Viral Immunology, Helmholtz Centre for Infection Research, Hannover-Braunschweig Site, 38124 Braunschweig, Germany; Centre for Individualized Infection Medicine, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
⁵ Aarhus Institute of Advanced Studies, Aarhus University, 8000 Aarhus, Denmark.
⁶ Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁷ Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany; Cluster of Excellence - Resolving Infection Susceptibility (RESIST, EXC 2155), Hannover Medical School, Hannover, Germany.
⁸ Aarhus Institute of Advanced Studies, Aarhus University, 8000 Aarhus, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
⁹ Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark. Electronic address: mrj@biomed.au.dk.

PMID: 40073016
DOI: 10.1016/j.celrep.2025.115413

Abstract

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⁺ T cell activation. Utilizing a culturing system with CD8⁺ T cells and autologous pDCs derived from circulating CD34⁺ hematopoietic stem and progenitor cells, we demonstrate that pDCs efficiently activate CD8⁺ 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⁺ 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⁺ T cell activation.

Keywords: CD8(+) T cell; CP: Immunology; IFNa; antigen presentation; dendritic cell; immunity; inflammation; pDC; plasmacytoid dendritic cell.