Early events in the thymus affect the balance of effector and regulatory T cells

Daniel J. Pennington (), Bruno Silva-Santos, Tobias Silberzahn, Mónica Escórcio-Correia, Martin J. Woodward, Scott J. Roberts, Adrian L. Smith, P. Julian Dyson and Adrian C. Hayday ()
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Daniel J. Pennington: King’s College London School of Medicine, Guy’s Hospital
Bruno Silva-Santos: King’s College London School of Medicine, Guy’s Hospital
Tobias Silberzahn: King’s College London School of Medicine, Guy’s Hospital
Mónica Escórcio-Correia: King’s College London School of Medicine, Guy’s Hospital
Martin J. Woodward: Institute of Child Health, University College
Scott J. Roberts: Yale University School of Medicine
Adrian L. Smith: Institute for Animal Health, Compton Laboratory
P. Julian Dyson: Imperial College, Hammersmith Hospital
Adrian C. Hayday: King’s College London School of Medicine, Guy’s Hospital

Nature, 2006, vol. 444, issue 7122, 1073-1077

Abstract: 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 γδ T cells into potent cytolytic and interferon-γ-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 γδ cell progenitors. Unexpectedly, we found that the propensity of early TCR-αβ+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in trans by CD4+CD8+ T-cell progenitor cells, before agonist selection.

Date: 2006
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DOI: 10.1038/nature06051

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