Stimulated plasmacytoid dendritic cells impair human T-cell development
| Autor: | 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 |
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| Přispěvatelé: | Clinical Immunology and Rheumatology, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Pathology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Cell Biology and Histology |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
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 |
| Zdroj: | Blood, 108(12), 3792-3800. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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