Macrophage colony stimulatory factor-activated bone marrow macrophages suppress lymphocytic responses through phagocytosis: a tentative in vitro model of Rosai-Dorfman disease.

NBXFO hybridoma cells produced macrophage colony-stimulating factor (M-CSF), which stimulated the growth of murine bone marrow-derived macrophages with potent suppressor activity. These macrophages suppressed lymphocyte responses to mitogens and antigens in a dose-dependent manner. Using a transwell chamber, we demonstrated that macrophages needed physical contact with the lymphocytes to suppress lymphocyte proliferation on day 1 in the concanavalin A mitogen reaction. In addition, no soluble suppressor factor was detected at that time. The number of lymphocytes disappeared with time when they were cocultured with the macrophages. Electron microscopy revealed that the macrophage phagocytosized the lymphocytes after 7 1/2 h. Dextran sulfate, heparan, and fucoidan prevented the macrophages from suppressing the lymphocytes. This phenomenon resembles the human disease sinus histiocytosis, also called Rosai-Dorfman disease, in which macrophages (histiocytes) phagocytosize autologous lymphocytes; occasionally, this disease is associated with immunological abnormalities. Thus we believed that macrophage-activating cytokines, such as M-CSF, may stimulate macrophages to phagocytose lymphocytes in vivo.