Spontaneous cytotoxicity of intestinal intraepithelial lymphocytes: clues to the mechanism

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Abstract
SUMMARY: Human intestinal intraepithelial lymphocytes (IEL) demonstrate target cell-restricted spontaneous cytotoxic (SC) activity that is due to CD2+CD3+CD8+CD16−CD56– effector eells: they kill epithelial cell (EC) tumours (such as DLD-1 colon cancer eells), but not natural killer (NK)-sensitive K-562 cells. The present study shows that the measured levels of SC activities by IEL correlated with those of autologous lamina propria lymphocytes (LPL), but not with those of peripheral blood lymphocytes (PBL). Also, the susceptibilities of DLD-1 cell clones to lysis by IEL and PBL effector cells did not correlate, suggesting different mechanisms of lysis. Antibody blocking experiments showed that the main surface molecules involved in lysis depended on the effector cell type: αEβt (HML-l) on IEL and CDI6 on PBL. No antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated by IEL, even after stimulation with inerferon-gamma (IFN-γ). Few IEL expressed Fc receptors for IgG. This study describes further differences between the SC activities of IEL and PBL.