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Regulatory T cell lineage commitment in the thymus

Ludger Klein1, Ksenija Jovanovic

  • 1University of Munich, Institute for Immunology, Goethestr. 31, 80336 Munich, Germany. ludger.klein@med.uni-muenchen.de

Seminars in Immunology
|July 8, 2011
PubMed

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.

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