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Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated Naïve T-cells.

التفاصيل البيبلوغرافية
العنوان: Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated Naïve T-cells.
المؤلفون: Eloho Etemire, Marco Krull, Mike Hasenberg, Peter Reichardt, Matthias Gunzer
المصدر: PLoS ONE, Vol 8, Iss 7, p e68378 (2013)
بيانات النشر: Public Library of Science (PLoS), 2013.
سنة النشر: 2013
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Regulatory T-cells (Tregs) are central for immune homeostasis and divided in thymus-derived natural Tregs and peripherally induced iTreg. However, while phenotype and function of iTregs are well known, a remarkable lack exists in knowledge about signaling mechanisms leading to their generation from naïve precursors in peripheral tissues. Using antigen specific naïve T-cells from mice, we investigated CD4+ CD25+ FoxP3- iTreg induction during antigen-specific T-cell receptor (TCR) stimulation with weak antigen presenting cells (APC). We show that early signaling pathways such as ADAM-17-activation appeared similar in developing iTreg and effector cells (Teff) and both initially shedded CD62-L. But iTreg started reexpressing CD62-L after 24 h while Teff permanently downmodulated it. Furthermore, between 24 and 72 hours iTreg presented with significantly lower phosphorylation levels of Akt-S473 suggesting lower activity of the PI3K/Akt-axis. This was associated with a higher expression of the Akt hydrophobic motif-specific phosphatase PHLPP1 in iTreg. Importantly, the lack of costimulatory signals via CD28 from weak APC was central for the development of regulatory function in iTreg but not for the reappearance of CD62-L. Thus, T-cells display a window of sensitivity after onset of TCR triggering within which the intensity of the PI3K/Akt signal controls entry into either effector or regulatory pathways.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874604/?tool=EBI; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0068378
URL الوصول: https://doaj.org/article/fa839ddb567e4b34a08d2d6690bfdd3a
رقم الأكسشن: edsdoj.fa839ddb567e4b34a08d2d6690bfdd3a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0068378