GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) COUNTERACTSTHE INHIBITING EFFECT OF MONOCYTES ON NATURAL-KILLER (NK) CELLS

GM-CSF is known to accelerate haematopoietic recovery following alloge neic bone marrow transplantation (BMT). In addition, it may restore an d enhance both granulocyte and monocyte functions. Stimulation of mono cyte functions may induce a direct or an indirect anti-leukaemic activ ity due to an increase of cellular cytotoxicity and production of cyto kines which may result in a reduction of the relapse rate after BMT. N K cells may play a crucial role in this activity. Therefore we studied the influence of monocytes on NK activity in combination with GM-CSF. Lymphocytes and monocytes were isolated from buffy coats of healthy i ndividuals by counterflow centrifugation elutriation (CCE). NK activit y was exerted by CD3(-)CD56(+) cell populations and could be enhanced by IL-2 incubation overnight. Incubation of CD3(-)CD56(+) cells with G M-CSF in the presence or absence of IL-2 hardly influenced NK activity of the lymphocyte population. Low amounts of monocytes enhanced NK ac tivity. NK activity in lymphocyte population in the presence of equiva lent numbers of monocytes with or without IL-2 was strongly decreased irrespective of the effector:target ratio (ETR). This appeared not to result from sterical hindrance effects of the present number of cells. However, addition of GM-CSF abrogated the inhibition of NK activity b y monocytes in the presence of IL-2. In monocyte fractions neither IL- 2 nor GMCSF yielded NK activity. Our findings indicate that GM-CSF can affect NK activity by counteracting the suppressing effects of monocy tes, and hence may improve the outcome after BMT.