Early Events in the Thymus Affect the Balance of Effector and Regulatory T Cells.
From: Peter Gorer Department of Immunobiology, King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, UK. d.pennington@qmul.ac.uk
Nature
- Publish Date: Dec 2006
- ISSN: 1476-4687
- Volume: 444
- Issue: 7122
- Pages: 1073-7
- Medium: Internet
- Language: English
- Citation (JAMA): Pennington Daniel J, Silva-Santos Bruno, Silberzahn Tobias, et al. Early Events in the Thymus Affect the Balance of Effector and Regulatory T Cells.. Nature Dec 2006;444:1073-7
Abstract
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.
Mesh Headings (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
Check for Full Text / PubMed Unique Identifier (PMID): 17190001
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