Ultrastructure of human natural killer cells: nature of the cytolytic contacts in relation to cellular secretion.

Abstract

The ultrastructure of human NK cells, NK/target cell conjugates, and the effect of monensin, a secretion inhibitor, were studied. Human peripheral blood lymphocytes, highly enriched (75 to 85%) in large granular lymphocytes (LGL), which are known to be the mediators of human NK activity, were used as effectors, and K562 cells as targets. LGL-type of cells were characterized in electron microscopy by a low nucleocytoplasmic ratio, indented nucleus, several large mitochondria, prominent Golgi apparatus, and cytoplasmic osmiophilic granules bound by a unit membrane. Their surface was of intermediate villous type. Two types of effector/target contacts were seen: either effector cell protrusions were pushed deep into pouches and lacunae of the target cell surface, or a wide area of intimate cell-to-cell contact was formed. The contact formation was followed by polarization of the effector cell Golgi apparatus towards the contact area. Monensin, a carboxylic ionophore, which interrupts the vesicular traffic of Golgi-derived vacuoles to the cell surface, caused an accumulation of cytoplasmic vesicles in the LGL but had no effect on the effector/target contact formation. Monensin inhibited the NK lysis apparently via cessation of secretion by the LGL. It did not affect the viability of the effector cells. The lytic steps of human NK cells thus involve binding to the target cell, polarization of cytoplasmic organelles towards the target, and apparently a precisely directed exocytosis of secretory material.