Fas-independent apoptosis of T cells via killer cell inhibitory receptors.

Abstract

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.