CYTOKINE-INDUCED CYTOTOXIC FUNCTION EXPRESSED BY LYMPHOCYTES OF THE INNATE IMMUNE-SYSTEM - DISTINGUISHING CHARACTERISTICS OF NK AND LAK BASED ON FUNCTIONAL AND MOLECULAR MARKERS

Several molecular events are now identifiable during the activation, r ecognition, and killing by natural killer (NK) cells that are distinct from those differentiated in response to cytokines during the generat ion of lymphokine-activated killer (LAK) cells or during lymphocyte pr oliferation. Because LAK and MHC-unrestricted killing activities also include the prototypic NK targets as part of their broad recognition s pectra, accurate identification of the complete function being studied is critical. In many publications, past and present, only NK-sensitiv e target cells were used (K562, Molt-4, others), and, therefore, the r esults do not necessarily indicate whether the effecters are NK or hav e differentiated into LAK cells. Such a consideration becomes critical when the effecters are grown in interleukin-2 (IL-2), and an attempt is made to define receptor recognition, signal transduction pathways, and specificity at the molecular level. In some instances, effector ce lls are likely to have stopped, therefore merely expressing NK activit y, and have also acquired LAK function. The identified receptors may n ot have been unique to NK cells or NK function. Not until the targets employed are also confirmed to be NK sensitive, and the effecters do n ot kill NK-resistant targets can the results of molecular studies be p roposed to represent aspects unique to NK. Reports of the use of IL-2- expanded NK clones are most likely providing data concerning the biolo gy of LAK and not of classic NK. The classic NK activity surveying our blood apparently performs an important function, including the abilit y to respond rapidly to certain cytokines and to acquire additional fu nctions and receptors for use in destroying a vast array of target cel ls. It is critical for scientists to appreciate the functional distinc tions and to identify the molecules and pathways unique to each of the se curious cytolytic systems.