Stimulation of immune-suppressive bone marrow cells by colony-stimulating factors

In previous studies, we demonstrated that immune-suppressive bone marrow cells appeared during a period of myelopoietic stimulation in mice bearing Lewis lung carcinoma (LLC) tumors and could be induced from normal bone marrow cells during 3 days of culture with supernatants of LLC variant cells. We have now shown that the capacity of LLC variants to induce immune suppressor cells was associated with the capacity to produce colony-stimulating factor (CSF) activities. The LLC variants that secreted more CSF activities also produced more bone marrow immune suppressor cell-inducing activity. The induction of immune-suppressive bone marrow cells was dependent on bone marrow cell proliferation because irradiation of bone marrow cells prior to culture with the CSF-containing supernatants blocked induction of suppressor cells. Culture supernatants of WEHI-3 cells and of pokeweed mitogen-stimulated spleen cells, rich sources of interleukin 3 (IL-3) and granulocyte-monocyte-CSF (GM-CSF), as well as recombinant mouse GM-CSF and recombinant mouse IL-3, also stimulated bone marrow suppressor cell activity. The combination of GM-CSF with IL-3 resulted in a synergistic rather than simply an additive induction of bone marrow suppressor cells. Conditioned medium of CSF-1-producing L cells did not induce bone marrow immune suppressor cells. These results suggest that during heightened periods of myelopoiesis, induction of bone marrow-derived immune suppressor cells may be stimulated by CSFs, such as by the singular or combined effects of GM-CSF and IL-3.