IL-2 ACTIVATED KILLER CELLS DISTINCT FROM NK AND T CELLS the top with a Pasteur pipette , and washed in CM

The lymphokine-activated killer cell (LAK) 1 system has been reported by us to represent a cytotoxic phenomenon distinct from either the classic cytotoxic thymusderived lymphocyte (CTL) or natural killer (NK) cell system on the basis of development kinetics, stimulus requirement, cytotoxic specificity, precursor location, and serologic phenotype of the LAK effector cells (1). The LAK system is unique in its simplicity of activation, since culture of nonadherent peripheral blood lymphocytes (PBL) for a minimum of 3 d in lectin-free lymphokine preparations rich in interleukin2 (IL-2) is the only requirement. As described earlier (1), the LAK phenomenon involves an activation mechanism that may be common to the many reports of nonclassic culture-induced lymphocyte-mediated cytotoxicities such as the mixed lymphocyte/leukocyte culture induced anomalous killers (2-6), NK-like killers (7, 8), fetal calf serum-induced killers (9-11), and lectin-induced killer cells (12). Therefore, this system is a most likely candidate for unifying the growing body of literature concerning these cytotoxicities, and for approaching the study of their biological significance. LAK can be generated from PBL of >90% of the cancer patients tested. One potential significance of the LAK cells is that they can efficiently lyse fresh single-cell suspensions of autologous fresh tumor cells, in addition to allogeneic fresh tumors and all cultured tumors tested, including those that are NK-resistant (1, 13), all of which LAK lyse optimally in a 4-h chromium-release assay. Since as yet no reproducible or consistent method is available for generation of human antitumor CTL, the potential for LAK as an important antitumor defense mechanism has encouraged further definition of the system. We have shown previously that the precursor of the LAK cell is nonadherent to plastic or nylon wool, and that its activation can be prevented by 2,000 rad of gamma irradiation. Therefore we studied in parallel the phenotype of the effectors and precursors of LAK cells, NK cells, and CTL and confirmed the distinct functional nature of each system by simultaneous activation cultures and