Monocyte-induced human natural killer cell suppression followed by increased cytotoxic activity during short-term in vitro culture in autologous serum.

ABSTRACT

When normal human peripheral blood mononuclear cells were tissue-cultured in autologous serum under conditions permitting cell contact, spontaneous fluctuations in cytotoxic activity were found. An analysis demonstrated that monocytes have the capacity to suppress initially (days 1-2) natural killer (NK) activity and that, at later time points (days 3-7), cytotoxic activity against the NK-susceptible target cell Molt-4 occurs which increases above initial NK levels. The newly induced killing depended on adequate cell contact for its induction and correlated with spontaneous proliferation in the cultures. The monocyte-induced NK suppression was found to be independent of cell contact and inhibited by the presence of indomethacin, thus most probably mediated by secreted prostaglandins. Suppressed NK cells (at day 1) had a lower number of target-binding cells (TBCs) and a smaller fraction of active NK cells among TBCs as compared with control cells. The fluctuations in cytotoxicity as seen in the present in vitro system are discussed in relation to clinical conditions with decreased NK activity, such as multiple sclerosis and Hodgkin's disease.