Fas-independent apoptosis of T cells via killer cell inhibitory receptors.
Killer cell inhibitory receptor (KIR) is expressed on NK cells and T cells, and negatively regulates the recognition of these cells via its binding to HLA class I molecules. Here we show the evidence that KIR is involved in apoptosis of T cells. The triggering of NKB1 molecules using DX9 anti-NKB1 mAb induced apoptosis of the cytotoxic T lymphocyte (CTL) clone expressing NKB1. Moreover, the cross-linking of NKB1 molecules together with CD3 molecules enhanced the apoptosis. The CTL clone carries Fas molecules, but failed to express Fas ligand (FasL) even after the cross-linking of both NKB1 and CD3 molecules. The apoptosis of the CTL clone induced by the cross-linking of both NKB1 and CD3 molecules was inhibited by IL-1beta-converting enzyme (ICE) inhibitor. These results together indicate that the apoptosis of CTL induced by the triggering of NKB1 molecules is not Fas-mediated but is linked to other signaling pathways using the ICE-like protease cascade.
Nakajima
H
H
Department of Tumor Biology, Institute of Medical Science, University of Tokyo, Japan.
Yamada
N
N
Takiguchi
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D013601:T-Lymphocytes / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D019014:fas Receptor