Human large granular lymphocytes and natural killing: Ultrastructural studies of strontium‐induced degranulation

Abstract

Large granular lymphocytes (LGL) are a subpopulation of human peripheral blood mononuclear cells believed to contain the mediators of spontaneous cytotoxicity or natural killing. In the present study, the mononuclear cells were enriched for LGL by differential density centrifugation on Percoll gradients and examined by transmission electron microscopy. The ultrastructure of LGL and of their binding interaction with natural killer‐susceptible target cells (K562) is described in detail. Some morphological similarity between LGL and cells of a myelocytic origin was observed. Studies reported elsewhere have shown that Sr²⁺, an alkaline earth ion known to degranulate granulocytes, inhibits NK cell function. Comparison of the morphology of control and Sr²⁺‐treated LGL showed that Sr²⁺ caused several characteristic changes in LGL ultrastructure and, indeed, led to their degranulation. The recovery of natural killer function seen following in vitro culture of Sr²⁺‐treated effector cells was accompanied by the reappearance of typical intracytoplasmic granules. These data strongly suggest that the granules of LGL are required for and, perhaps, involved in natural killer‐mediated cytolysis.