REGULATION OF NATURAL-KILLER FUNCTION BY NONLYMPHOID CELLS

Natural killer (NK) cells and interleukin-2 activated NK cells, termed lymphokine-activated killer (LAK) cells, can lyse tumor cells without restriction by the MHC complex. The cytotoxic activity of these cells is subject to regulation by nonlymphoid cells in vitro. Interaction o f NK cells with red blood cells (RBC) increases NK cytotoxicity. Inter action with polymorphonuclear neutrophils (PMN) suppresses LAK develop ment and also inhibits NK- and LAK-mediated cytotoxicity at the effect or cell phase. Exposure to tumor necrosis factor-a greatly enhances th e inhibitory effect of PMN at the effector cell phase. Depending on th eir states of activation and differentiation, monocytes have the capac ity to either enhance or suppress LAK induction. In contrast, macropha ges derived from the lung are potent inhibitors of NK and LAK activity at both the induction and effector cell phases. Several cytokines are secreted by monocytes and macrophages and these include both suppress ive and enhansive factors of cytotoxic function. Platelets are also ca pable of releasing suppressive factors. NK cells are believed to be in volved in host surveillance of tumors, control of microbial infections and regulation of hematopoiesis. Regulation of NK cells by nonlymphoi d cells and their products likely provides an in vivo mechanism for lo cally regulating NK function.