title: Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments.
abstract: During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: van Meerwijk
authors.forename: T
authors.initials: T
authors.lastname: Bianchi
authors.forename: S
authors.initials: S
authors.lastname: Marguerat
authors.forename: H R
authors.initials: HR
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013045:Species Specificity; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta