1. Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8(+) T cells despite lower Ag uptake than myeloid dendritic cell subsets
- Author
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Luis J. Cruz, Sonja I. Buschow, Annechien J. A. Lambeck, Gerty Schreibelt, Carl G. Figdor, I. Jolanda M. de Vries, Till S.M. Mathan, Jurjen Tel, and Simone P. Sittig
- Subjects
CD4-Positive T-Lymphocytes ,Myeloid ,Thrombomodulin ,Immunology ,CD16 ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,GPI-Linked Proteins ,Biochemistry ,Antigens, CD1 ,03 medical and health sciences ,Interferon-gamma ,0302 clinical medicine ,Antigen ,Immune Regulation [NCMLS 2] ,Antigens, Neoplasm ,Neoplasms ,MHC class I ,medicine ,Cytotoxic T cell ,Humans ,Myeloid Cells ,Cells, Cultured ,030304 developmental biology ,Glycoproteins ,0303 health sciences ,Antigen Presentation ,biology ,Follicular dendritic cells ,Chemistry ,Receptors, IgG ,Translational research Immune Regulation [ONCOL 3] ,hemic and immune systems ,Cell Biology ,Hematology ,Dendritic Cells ,Acquired immune system ,Immunity, Innate ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Solubility ,Antigens, Surface ,biology.protein ,Immunotherapy ,CD8 ,030215 immunology - Abstract
Contains fulltext : 118559.pdf (Publisher’s version ) (Open Access) In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16(+), CD1c(+), and BDCA-3(+) myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8(+) T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c(+) and BDCA3(+) mDCs, pDCs induce potent Ag-specific CD4(+) and CD8(+) T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4(+) and CD8(+) T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3(+) mDCs. These findings, and the fact that pDCs outnumber BDCA3(+) mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8(+) T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.
- Published
- 2013
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