Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes.
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.
Kojima
H
H
Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Shinohara
N
N
Hanaoka
S
S
Someya-Shirota
Y
Y
Takagaki
Y
Y
Ohno
H
H
Saito
T
T
Katayama
T
T
Yagita
H
H
Okumura
K
K
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
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin