The magnitude of thymic output is genetically determined through controlled intrathymic precursor T cell proliferation.
The thymus plays a crucial role in providing the immune system with naive T cells showing a diverse TCR repertoire. Whereas the diversity of thymic production is mainly ensured by TCR rearrangement at both the TRA and TRB loci, the number of cells reaching the double-positive differentiation stage defines the extent of thymic output. A quantitative analysis of TCR excision circles (TREC; signal-joint TRECs and DJbetaTRECs) produced at different stages of thymopoiesis was performed in nine laboratory mouse strains. The results clearly demonstrate that the magnitude of thymic output is directly proportional to the extent of proliferation in the double-negative 4 thymocyte subset. Strikingly, intrathymic precursor T cell proliferation was found to be strain dependent, thus suggesting a genetic regulation of thymic output. The inherited character of thymic output was further confirmed by the transmission of the phenotype in a recessive fashion in F(1) progeny of the different parental strains. Our results provide the first demonstration of the genetic regulation of thymic output.
Dulude
Gaël
G
Laboratoire d'Immunologie, Centre de Recherches du Centre Hospitalier de l'Université Montréal, Saint-Luc, Montréal, Québec, Canada.
Cheynier
Remi
R
Gauchat
Dominique
D
Abdallah
Ali
A
Kettaf
Nadia
N
Sékaly
Rafick-Pierre
RP
Gratton
Sophie
S
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D003433:Crosses, Genetic; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D040641:Quantitative Trait Loci / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta