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Letter
Nature 444, 1073-1077 (21 December 2006) | doi:10.1038/nature06051; Received 6 September 2006; Accepted 24 October 2006; Published online 12 November 2006
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Early events in the thymus affect the balance of effector and regulatory T cells
Daniel J. Pennington1,2, Bruno Silva-Santos1,3, Tobias Silberzahn1, Mónica Escórcio-Correia1, Martin J. Woodward4, Scott J. Roberts5, Adrian L. Smith6, P. Julian Dyson7 & Adrian C. Hayday1
- Peter Gorer Department of Immunobiology, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK
- Institute of Cell and Molecular Science, The London and Barts School of Medicine and Dentistry, Queen Mary College, London E1 2AT, UK
- Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa 1649-028, Portugal
- Molecular Haematology and Cancer Biology Unit, Camelia Botnar Laboratories, Institute of Child Health, University College, London WC1N 1EH, UK
- Department of Dermatology, 15 York Street HRT 603, Yale University School of Medicine, New Haven, Connecticut 06510, USA
- Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berks RG20 7NN, UK
- Division of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
Correspondence to: Daniel J. Pennington1,2Adrian C. Hayday1 Correspondence and requests for materials should be addressed to D.J.P. (Email: d.pennington@qmul.ac.uk) or A.C.H. (Email: adrian.hayday@kcl.ac.uk).
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) cells1, 2, 3. 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) ligands4, 5, 6. 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 
T cells into potent cytolytic and interferon-
-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 
cell progenitors. Unexpectedly, we found that the propensity of early TCR-
+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in trans by CD4+CD8+ T-cell progenitor cells, before agonist selection.
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