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, recognition, and killing by natural killer (NK) cells that are distinct from those differentiated in response to cytokines during the generation of lymphokine-activated killer (LAK) cells or during lymphocyte proliferation. Because LAK and MHC-unrestricted killing activities also include the prototypic NK targets as part of their broad recognition spectra, accurate identification of the complete function being studied is critical. In many publications, past and present, only NK-sensitive target cells were used (K562, Molt-4, others), and, therefore, the results do not necessarily indicate whether the effectors are NK or have differentiated into LAK cells. Such a consideration becomes critical when the effectors 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 cells are likely to have stopped, therefore merely expressing NK activity, and have also acquired LAK function. The identified receptors may not have been unique to NK cells or NK function. Not until the targets employed are also confirmed to be NK sensitive, and the effectors do not kill NK-resistant targets can the results of molecular studies be proposed to represent aspects unique to NK. Reports of the use of IL-2-expanded NK clones are most likely providing data concerning the biology of LAK and not of classic NK. The classic NK activity surveying our blood apparently performs an important function, including the ability to respond rapidly to certain cytokines and to acquire additional functions and receptors for use in destroying a vast array of target cells. It is critical for scientists to appreciate the functional distinctions and to identify the molecules and pathways unique to each of these curious cytolytic systems.