title: CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny.
abstract: During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8+ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.
authors.affiliation: Ontario Cancer Institute, Toronto, Canada.
authors.forename: W P
authors.initials: WP
authors.lastname: Fung-Leung
authors.forename: V A
authors.initials: VA
authors.lastname: Wallace
authors.forename: D
authors.initials: D
authors.lastname: Gray
authors.forename: W C
authors.initials: WC
authors.lastname: Sha
authors.forename: H
authors.initials: H
authors.lastname: Pircher
authors.forename: H S
authors.initials: HS
authors.lastname: Teh
authors.forename: D Y
authors.initials: DY
authors.lastname: Loh
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000032:analysis / Q000502:physiology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
chemical_list: D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell