title: Clonal deletion of major histocompatibility complex class I-restricted CD4+CD8+ thymocytes in vitro is independent of the CD95 (APO-1/Fas) ligand.
abstract: The CD95 (APO-1/Fas) ligand (CD95L) mediates apoptosis in sensitive target cells, Ca(2+)-independent cytotoxicity of cells from perforin knock-out mice, and peripheral deletion of activated T cells through engagement of its cognate receptor CD95. Double-positive thymocytes show a high constitutive expression of CD95. Therefore, we used a model system and investigated whether negative selection through apoptosis might involve CD95/CD95L. We analyzed whether CD95L may induce antigen-specific deletion of double-positive thymocytes from mice transgenic for a lymphocytic choriomeningitis virus (LCMV)/H2b-specific T cell receptor (TCR). These cells are deleted in vitro upon addition of the LCMV-peptide 33-41 in a major histocompatibility complex-class I-restricted fashion. Deletion was not blocked by soluble mouse and human CD95-Fc receptor decoys. CD95-Fc receptor decoys, however, were effective in blocking apoptosis induced by mouse CD95L-transfected L929 cells in sensitive CD95+ target cells and in thymocytes. These results suggest that TCR-induced deletion of immature thymocytes in vitro is independent of CD95L. Thus, our data argue against a role of CD95L in negative selection of MHC-class I-restricted autoreactive thymocytes.
authors.affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Müller
authors.forename: S M
authors.initials: SM
authors.lastname: Mariani
authors.forename: B
authors.initials: B
authors.lastname: Matiba
authors.forename: B
authors.initials: B
authors.lastname: Kyewski
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D015704:CD4 Antigens; D016827:CD8 Antigens; D002478:Cells, Cultured; D017637:Clonal Deletion; D053222:Fas Ligand Protein; D006183:H-2 Antigens / Q000276:immunology; D006801:Humans; D007739:L Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D019014:fas Receptor