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

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Abstract
The role of recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in monocyte‐mediated up‐regulation of lymphokine‐activated killer (LAK) ell 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 5lCr‐release assay. For determination of the role of GM‐CSF in LAK induction, highly purified lymphocytes (>99%) and monocytes (>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 upregulation of LAK cell induction in vivo.

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