1. Peter Gorer Department of Immunobiology, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK
2. Institute of Cell and Molecular Science, The London and Barts School of Medicine and Dentistry, Queen Mary College, London E1 2AT, UK
3. Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa 1649-028, Portugal
4. Molecular Haematology and Cancer Biology Unit, Camelia Botnar Laboratories, Institute of Child Health, University College, London WC1N 1EH, UK
5. Department of Dermatology, 15 York Street HRT 603, Yale University School of Medicine, New Haven, Connecticut 06510, USA
6. Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berks RG20 7NN, UK
7. Division of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK

Correspondence to: Daniel J. Pennington^1,2Adrian 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 (T_r) cells^{1, 2, 3}. Thus, many studies have focused on the developmental origin of T_r 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^{4, 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⁺ T_r cells is also regulated in trans by CD4⁺CD8⁺ T-cell progenitor cells, before agonist selection.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.