Early events in the thymus affect the balance of effector and regulatory T cells.
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.
Pennington
Daniel J
DJ
Peter Gorer Department of Immunobiology, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK. d.pennington@qmul.ac.uk
Silva-Santos
Bruno
B
Silberzahn
Tobias
T
Escórcio-Correia
Mónica
M
Woodward
Martin J
MJ
Roberts
Scott J
SJ
Smith
Adrian L
AL
Dyson
P Julian
PJ
Hayday
Adrian C
AC
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D013997:Time Factors
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta