title: Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice.
abstract: Although mature CD4+ T cells bear T cell receptors (TCRs) that recognize class II major histocompatibility complex (MHC) and mature CD8+ T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of the TCR. According to this model, CD4+ cells with class I TCR do not mature because the CD8 coreceptor is required for class I MHC recognition and positive selection. If this model is correct, constitutive expression of CD8 should allow CD4+ T cells with class I-specific TCRs to develop. In this report, we show that mature peripheral CD4+ cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-selected CD4 population, including the ability to express CD40 ligand upon activation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II MHC. These results indicate that some T cells choose the CD4 helper lineage independent of their antigen receptor specificity; however, the inefficiency of generating class I-specific CD4 cells leaves open the possibility that an instructive signal generated upon MHC recognition may bias lineage commitment.
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley 94720.
authors.forename: E
authors.initials: E
authors.lastname: Robey
authors.forename: A
authors.initials: A
authors.lastname: Itano
authors.forename: W C
authors.initials: WC
authors.lastname: Fanslow
authors.forename: B J
authors.initials: BJ
authors.lastname: Fowlkes
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D019013:CD40 Antigens; D016827:CD8 Antigens / Q000096:biosynthesis*; D005434:Flow Cytometry; D015870:Gene Expression; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015704:CD4 Antigens; D019013:CD40 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II