title: A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat.
abstract: During their development, immature CD4CD8 double positive thymocytes become committed to either the CD4 or CD8 lineage. The final size of the peripheral CD4 and CD8 T cell compartments depends on thymic output and on the differential survival and proliferation of the respective T cell subsets in the periphery. Our results reveal that the development of the distinct peripheral 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 determined 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 selection in the thymus.
authors.affiliation: Department of Internal Medicine, Section Immunology, University Maastricht, The Netherlands. jgmc.damoiseaux@immuno.unimaas.nl
authors.forename: J G
authors.initials: JG
authors.lastname: Damoiseaux
authors.forename: B
authors.initials: B
authors.lastname: Cautain
authors.forename: I
authors.initials: I
authors.lastname: Bernard
authors.forename: M
authors.initials: M
authors.lastname: Mas
authors.forename: P J
authors.initials: PJ
authors.lastname: van Breda Vriesman
authors.forename: P
authors.initials: P
authors.lastname: Druet
authors.forename: G
authors.initials: G
authors.lastname: Fournié
authors.forename: A
authors.initials: A
authors.lastname: Saoudi
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D011828:Radiation Chimera / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens