Dendritic Cells Require STAT-1 Phosphorylated at Its Transactivating Domain for the Induction of Peptide-Specific CTL
| Autor: | Karen Lingnau, Veronika Sexl, Ulrich Kalinke, Alexander von Gabain, Wolfgang Kratky, Thomas Rülicke, Thomas Kolbe, Mathias Müller, Andreas Pilz, Dagmar Stoiber, Olivia Simma, Silvia Stockinger, Thomas Decker |
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| Rok vydání: | 2009 |
| Předmět: |
Adoptive cell transfer
T cell Immunology Epitopes T-Lymphocyte Mice Transgenic Immunopotentiator Biology Lymphocyte Activation Mice Serine medicine Animals Homeostasis Immunology and Allergy Transcription factor Cell Proliferation Mice Knockout Cell Differentiation Dendritic Cells Dendritic cell Cytotoxicity Tests Immunologic Molecular biology Peptide Fragments Protein Structure Tertiary Cell biology Mice Inbred C57BL CTL STAT1 Transcription Factor medicine.anatomical_structure Trans-Activators Phosphorylation CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 183:2286-2293 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Phosphorylation of transcription factor STAT-1 on Y701 regulates subcellular localization whereas phosphorylation of the transactivating domain at S727 enhances transcriptional activity. In this study, we investigate the impact of STAT-1 and the importance of transactivating domain phosphorylation on the induction of peptide-specific CTL in presence of the TLR9-dependent immune adjuvant IC31. STAT-1 deficiency completely abolished CTL induction upon immunization, which was strongly reduced in animals carrying the mutation of the S727 phospho-acceptor site. A comparable reduction of CTL was found in mice lacking the type I IFN (IFN-I) receptor, whereas IFN-γ-deficient mice behaved like wild-type controls. This finding suggests that S727-phosphorylated STAT-1 supports IFN-I-dependent induction of CTL. In adoptive transfer experiments, IFN-I- and S727-phosphorylated STAT-1 were critical for the activation and function of dendritic cells. Mice with a T cell-specific IFN-I receptor ablation did not show impaired CTL responses. Unlike the situation observed for CTL development S727-phosphorylated STAT-1 restrained proliferation of naive CD8+ T cells both in vitro and following transfer into Rag-deficient mice. In summary, our data reveal a dual role of S727-phosphorylated STAT-1 for dendritic cell maturation as a prerequisite for the induction of CTL activity and for T cell autonomous control of activation-induced or homeostatic proliferation. |
| Databáze: | OpenAIRE |
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