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In cellular immunology the critical balance between effector and regulatory mechanisms is highlighted by serious immunopathologies attributable to mutations in Foxp3, a transcription factor required for a major subset of regulatory T (Tr) cells. Thus, many studies have focused on the developmental origin of Tr cells, with the prevailing view that they emerge in the thymus from late-stage T-cell progenitors whose T-cell receptors (TCRs) engage high affinity (agonist) ligands. This study questions the completeness of that interpretation. Here we show that without any obvious effect on TCR-mediated selection, the normal differentiation of mouse gammabeta T cells into potent cytolytic and interferon-gamma-secreting effector cells is switched towards an aggregate regulatory phenotype by limiting the capacity of CD4+CD8+ T-cell progenitors to influence in trans early gammabeta cell progenitors. Unexpectedly, we found that the propensity of early TCR-alphabeta+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in trans by CD4+CD8+ T-cell progenitor cells, before agonist selection.

Original publication

DOI

10.1038/nature06051

Type

Journal article

Journal

Nature

Publication Date

21/12/2006

Volume

444

Pages

1073 - 1077

Keywords

Animals, Cell Count, Cell Differentiation, Forkhead Transcription Factors, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, Stem Cells, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Thymus Gland, Time Factors