title: Regulatory T cell lineage commitment in the thymus.
abstract: A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell repertoire is generated through instructive and/or selective processes in the thymus, and there is some consensus that clonal deviation into the T(reg) lineage is a result of self-antigen recognition. Paradoxically, the same holds true for a diametrically different cell fate decision of developing thymocytes, namely their removal from the repertoire through apoptotic cell death (clonal deletion). Here, we will review our current understanding of how T cell receptor stimulation, cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic developmental tuning synergize during T(reg) cell differentiation, and how instructive signals converge at the Foxp3 gene-locus during entry into the T(reg) cell lineage. We will also discuss how these parameters relate to known determinants of negative selection.
authors: University of Munich, Institute for Immunology, Goethestr. 31, 80336 Munich, Germany. ludger.klein@med.uni-muenchen.de
authors: Ludger
authors: L
authors: Klein
authors: Ksenija
authors: K
authors: Jovanovic
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D019070:Cell Lineage; D044127:Epigenesis, Genetic; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*