title: Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes.
abstract: To study the contribution of putative perforin-independent mechanism in the antigen-specific target destruction by cytotoxic T lymphocytes CD8+ CTL lines were established from spleen cells of chimeric mice produced by injecting perforin (-/-) embryonic stem cells into blastocysts of RAG-2(-/-) mice. When tested on normal concanavalin A blasts, these perforin-deficient cytotoxic T lymphocyte lines were found to be capable of inducing antigen-specific target cell lysis accompanied by DNA degradation. In contrast, with target cells carrying a mutation in Fas molecule, perforin-independent cytotoxicity was not detectable. These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis.
authors.affiliation: Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: N
authors.initials: N
authors.lastname: Shinohara
authors.forename: S
authors.initials: S
authors.lastname: Hanaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Someya-Shirota
authors.forename: Y
authors.initials: Y
authors.lastname: Takagaki
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Katayama
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000502:physiology; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin