J. Atzpodien et Sc. Gulati, T-CELLS AND MONOCYTES REGULATE THE GENERATION AND FUNCTIONAL-ACTIVITYOF NATURAL KILLER-DERIVED LYMPHOKINE-ACTIVATED KILLER-CELLS, Stem cells, 11(6), 1993, pp. 511-518
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.