Up-regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of induction of lymphokine (IL-2)-activated killer (LAK) cells by human blood monocytes.

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by IL-2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells, as assessed by the 4 hr 51Cr-release assay. For determination of the role of GM-CSF in LAK induction, highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated from MNC by counter-flow centrifugal elutriation (CCE). Pre-treatment of monocytes for 4 days with GM-CSF before addition of lymphocytes plus IL-2 resulted in a significant dose-dependent increase in monocyte-mediated up-regulation of LAK induction, but in the absence of monocytes GM-CSF had no effect on LAK cell induction. Similarly, GM-CSF augmented the proliferative response of lymphocytes to IL-2 in the presence of monocytes as assessed by 3H-TdR uptake. Treatment with anti-GM-CSF antibody completely abolished up-regulation of LAK induction by GM-CSF-treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM-CSF-responding monocytes were found to be responsible for up-regulation of LAK induction. These results suggest that GM-CSF may be important in monocyte-mediated up-regulation of LAK cell induction in vivo.