Abstract
Lymphokine activated killer (LAK) cells are generated by a culture of lymphocytes with interleukin 2 (IL 2) without the need for any additional antigenic stimulation. LAK cells can lyse a wide spectrum of allogeneic and syngeneic tumor cells regardless of whether the tumor target cells are sensitive or resistant to fresh natural killer (NK) cells. In these studies, the functional characteristics of LAK cells by using metabolic inhibitors were investigated. The following results were obtained:
(1) Human peripheral blood lymphocytes were cultured in the presence of 2units/ml of human recombinant IL 2 (TGP-3, Takeda, Osaka), the dose of which is routinely used for the activation of LAK cells in human pilot studies. The killing activity was generated within 4 days and continued for more than 14 days.
(2) LAK cells generated by a higher dose of rIL 2 (2units/ml), are resistant to inhibitors for lipid peroxidation such as dimethylsulfoxide, ethyl alcohol, and nordihydroguaiaretic acid, while NK lineage killers such as fresh NK cells and killer cells activated by a lower dose of rIL 2 (approximately 0.02unit/ml) according to the method of Itoh et al. are sensitive to those reagents.
It is concluded that LAK cells induced by a relatively higher dose of rIL 2 have different lytic pathways from killer cells of NK lineage, and LAK activity appears to be derived from phenotypically heterogenous population and confined to any single subpopulation.
