THYMIC LINEAGE COMMITMENT RATHER THAN SELECTION CAUSES GENETIC VARIATIONS IN SIZE OF CD4 AND CD8 COMPARTMENTS

During their development, immature CD4(+)CD8(+) thymocytes become comm itted to either the CD4 or CDS Lineage, Subsequent complete maturation of CD4(+) and CD8(+) cells requires a molecular match of the expresse d 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 c ell compartments shows marked genetic variability. We show here that g enetic variations in thymic lineage commitment, rather than TCR-mediat ed selection processes, are responsible for the distinct CD4/CD8 ratio s observed in common inbred mouse strains, Genetic variations in the r egulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.