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Nuclear transfer nTreg model reveals fate-determining TCR-[Beta] and novel peripheral nTreg precursors
Ist Teil von
Proceedings of the National Academy of Sciences - PNAS, 2016-04, Vol.113 (16), p.E2316
Ort / Verlag
Washington: National Academy of Sciences
Erscheinungsjahr
2016
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) ...-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR ...-chain was able to provide stronger TCR signals. This TCR-...-driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3- CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. (ProQuest: ... denotes formulae/symbols omitted.)