T-CELLS AND MONOCYTES REGULATE THE GENERATION AND FUNCTIONAL-ACTIVITYOF NATURAL KILLER-DERIVED LYMPHOKINE-ACTIVATED KILLER-CELLS

The lymphokine-activated killer (LAK) phenomenon is generally referred to as nonspecific, i.e., major histocompatibility complex (MHC)-unres tricted cytotoxicity against tumor cells generated by ex vivo culture of human peripheral blood lymphocytes with interleukin 2 (IL-2). In th is study, we selectively purified and depleted cell subpopulations suc h as natural killer (NK) cells, T-lymphocytes and monocytes from fresh human peripheral blood by negative selection. While highly purified N K cells could be induced to acquire potent LAK activity in five-day cu lture with IL-2, the presence of T-lymphocytes and monocytes in NK cul tures was needed in order to induce a significant expansion of cytotox ic effector cells over the culture period. Neither T cells nor monocyt es by themselves were able to generate LAK cells in a standard rive-da y IL-2 culture. However, when added to highly purified NK cells prior to IL-2 incubation, a proportion of CD3, T-lymphocytes was found to ga in LAK-like killing activity. Monocytes, when cultured with IL-2 in th e presence of NK cells and T-lymphocytes, did not appear to acquire LA K activity but were able to induce a dramatic increase in cytotoxic ly mphocyte recovery after five days with IL-2. In summary, we could demo nstrate that peripheral blood T-lymphocytes and monocytes are potent r egulators of NK-dependent lymphokine (IL-2)-activated killing.