A dominant role for the thymus anti MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat

During their development, immature CD4CD8 double positive thymocytes become committed to either the CD4 or CD8 lineage. The final size of the peripher al CD4 and CD8 T cell compartments depends on thymic output and on the diff erential survival and proliferation of the respective T cell subsets in the periphery. Our results reveal that the development of the distinct periphe ral CD4/CD8 T cell ratio between Lewis and Brown Norway rats originates in the thymus and, as shown by the use of radiation bone marrow chimeras, is d etermined by selection on radio-resistant stromal cells. Furthermore, this difference is strictly correlated with the MHC haplotype and is the result of a reduction in the absolute number of CD8 T cells in Brown Norway rats. These data suggest that the distinct CD4/CD8 T cell ratio between these two rat strains is the consequence of differential interactions of the TCR/CD8 coreceptor complex with the respective MHC class I haplotypes during selec tion in the thymus.