1. Stimulated plasmacytoid dendritic cells impair human T-cell development
- Author
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Monique E.C.M. Oud, Marcel Spaargaren, Heike Schmidlin, Fedde Groot, Wendy Dontje, Suzanne J. Ligthart, Arnaud D. Colantonio, Esther J. M. Schilder-Tol, Hergen Spits, Bianca Blom, Christel H. Uittenbogaart, Clinical Immunology and Rheumatology, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Pathology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Cell Biology and Histology
- Subjects
T-Lymphocytes ,Cellular differentiation ,T cell ,Plasma Cells ,Immunology ,Receptors, Antigen, T-Cell ,Thymus Gland ,Plasmacytoid dendritic cell ,Biology ,Biochemistry ,Antibodies ,Cell Line ,Mice ,Antigens, CD ,Bone Marrow ,medicine ,Animals ,Humans ,Progenitor cell ,Antigen-presenting cell ,Immunobiology ,Receptors, Interleukin-7 ,Interleukin-7 ,Stem Cells ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Cell Biology ,Hematology ,Dendritic cell ,Coculture Techniques ,Cell biology ,medicine.anatomical_structure ,Interferon Type I ,Stem cell ,Protein Kinases ,CD8 ,Signal Transduction - Abstract
Thymic plasmacytoid dendritic cells (pDCs) are located predominantly in the medulla and at the corticomedullary junction, the entry site of bone marrow-derived multipotential precursor cells into the thymus, allowing for interactions between thymic pDCs and precursor cells. We demonstrate that in vitro-generated pDCs stimulated with CpG or virus impaired the development of human autologous CD34(+)CD1a(-) thymic progenitor cells into the T-cell lineage. Rescue by addition of neutralizing type I interferon (IFN) antibodies strongly implies that endogenously produced IFN-alpha/beta is responsible for this inhibitory effect. Consistent with this notion, we show that exogenously added IFN-alpha had a similar impact on IL-7- and Notch ligand-induced development of thymic CD34(+)CD1a(-) progenitor cells into T cells, because induction of CD1a, CD4, CD8, and TCR/CD3 surface expression and rearrangements of TCRbeta V-DJ gene segments were severely impaired. In addition, IL-7-induced proliferation but not survival of the developing thymic progenitor cells was strongly inhibited by IFN-alpha. It is evident from our data that IFN-alpha inhibits the IL-7R signal transduction pathway, although this could not be attributed to interference with either IL-7R proximal (STAT5, Akt/PKB, Erk1/2) or distal (p27(kip1), pRb) events.
- Published
- 2006
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