Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity.
To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the involvement of apoptosis-inducing Fas molecule on the target cells and its ligand on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a CD4+ T-cell clone, BK1, could lyse the target cells expressing wild-type Fas molecule but not those expressing death signaling-deficient mutants. This indicates the involvement of Fas-mediated signal transduction in the target cell lysis by BK1. Anti-CD3-activated but not resting BK1 expressed Fas ligand as detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas ligand in the BK1 cytotoxicity. Ability to exert the Fas-mediated cytotoxicity was not confined to BK1, but splenic CD4+ T cells and, to a lesser extent, CD8+ T cells could also exert the Fas-dependent target cell lysis. This indicates that the Fas-mediated target cell lytic pathway can be generally involved in the T-cell-mediated cytotoxicity. Interestingly, CD4+ T cells prepared from gld/gld mice did not mediate the Fas-mediated cytotoxicity, indicating defective expression of functional Fas ligand in gld mice.
Hanabuchi
S
S
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Koyanagi
M
M
Kawasaki
A
A
Shinohara
N
N
Matsuzawa
A
A
Nishimura
Y
Y
Kobayashi
Y
Y
Yonehara
S
S
Yagita
H
H
Okumura
K
K
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004247:DNA; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D015398:Signal Transduction; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor
D000954:Antigens, Surface; D015704:CD4 Antigens; D008024:Ligands; D008565:Membrane Proteins; D019014:fas Receptor; D004247:DNA