Production of colony-stimulating factor in mixed leucocyte cultures.

Mixed leucocyte cultures (MLC) were prepared from mouse spleens, lymph nodes or human peripheral blood. After 4 days, media from these cultures contained markedly elevated levels of granulocyte/macrophage colony stimulating factor (CSF). If lymphocyte transformation and proliferation was prevented with mitomycin C or by using cell suspensions from congenitally athymic mice, no increased CSF production occurred. CSF was not detected until after 48 hours and lagged behind RNA, protein, and DNA synthesis. When spleen cells from mice undergoing a graft-versus-host (GvH) reaction were cultured alone there was also production of CSF. Whether lymphocytes responding to allogeneic cells produce CSF directly or stimulate macrophages to produce it is not clear. However, these results suggest a mechanism by which the granulocyte/macrophage system may be activated in immune responses that involve lymphocyte proliferation.