Stem Cells, Vol 11, 511-518, Copyright © 1993 by AlphaMed Press
T cells and monocytes regulate the generation and functional activity of natural killer-derived lymphokine-activated killer cells
J Atzpodien and SC Gulati
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
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.
