T cells and monocytes regulate the generation and functional activity of 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)-unrestricted cytotoxicity against tumor cells generated by ex vivo culture of human peripheral blood lymphocytes with interleukin 2 (IL-2). In this study, we selectively purified and depleted cell subpopulations such as natural killer (NK) cells, T-lymphocytes and monocytes from fresh human peripheral blood by negative selection. While highly purified NK cells could be induced to acquire potent LAK activity in five-day culture with IL-2, the presence of T-lymphocytes and monocytes in NK cultures was needed in order to induce a significant expansion of cytotoxic effector cells over the culture period. Neither T cells nor monocytes by themselves were able to generate LAK cells in a standard five-day 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 gain LAK-like killing activity. Monocytes, when cultured with IL-2 in the presence of NK cells and T-lymphocytes, did not appear to acquire LAK activity but were able to induce a dramatic increase in cytotoxic lymphocyte recovery after five days with IL-2. In summary, we could demonstrate that peripheral blood T-lymphocytes and monocytes are potent regulators of NK-dependent lymphokine (IL-2)-activated killing.
Atzpodien
J
J
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Gulati
S C
SC
D002450:Cell Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2