Dendritic Cells Require STAT-1 Phosphorylated at Its Transactivating Domain for the Induction of Peptide-Specific CTL

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Bibliographische Detailangaben
Zeitschriftentitel:	The Journal of Immunology
Personen und Körperschaften:	Pilz, Andreas, Kratky, Wolfgang, Stockinger, Silvia, Simma, Olivia, Kalinke, Ulrich, Lingnau, Karen, von Gabain, Alexander, Stoiber, Dagmar, Sexl, Veronika, Kolbe, Thomas, Rülicke, Thomas, Müller, Mathias, Decker, Thomas
In:	The Journal of Immunology, 183, 2009, 4, S. 2286-2293
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	The American Association of Immunologists
Schlagwörter:	Immunology Immunology and Allergy

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Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
Umfang:	2286-2293
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.0901383