title: Ligand-stimulated signaling events in immature CD4+CD8+ thymocytes expressing competent T-cell receptor complexes.
abstract: During thymic selection of the developing T-cell repertoire, the fate of individual CD4+CD8+ thymocytes is determined by the specificity of the T-cell antigen receptors (TCRs) they express. Paradoxically, most CD4+CD8+ thymocytes express few TCR molecules, and those they express are essentially incapable of transducing intracellular signals as measured by intracellular calcium mobilization. However, both TCR number and calcium-signaling capability are significantly induced in CD4+CD8+ thymocytes when the cells are released from intrathymic inhibitory signals that are mediated by their CD4 molecules. Here, the response to ligand engagement of TCR on "induced" CD4+CD8+ thymocytes that have been released from CD4-mediated inhibition was examined and was found to result in internalization of surface TCR complexes and rephosphorylation of zeta chains of the TCR complex. In addition, a proportion of induced CD4+CD8+ thymocytes were found to fragment their DNA upon ligand engagement. Thus, this study describes early events in immature CD4+CD8+ thymocytes resulting from TCR-mediated signals.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: L E
authors.initials: LE
authors.lastname: Samelson
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: T I
authors.initials: TI
authors.lastname: Munitz
authors.forename: M
authors.initials: M
authors.lastname: Sheard
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: A
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D015151:Immunoblotting; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008954:Models, Biological; D019000:Phosphotyrosine; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D014443:Tyrosine