The Induction of Macrophage Proliferation in Vitro by a Lymphocyte-Produced Factor

The studies presented indicate that sensitized guinea pig lymph node lymphocytes release on exposure to antigen a soluble mediator of 35 to 70,000 daltons, which induces proliferation of nonimmune oil-induced, monocyte-derived peritoneal and noninduced alveolar macrophages. Cell counts and nuclear labeling experiments indicate that this proliferation can be effectively assayed under conditions of monolayer culture by tritiated thymidine incorporation. The magnitude and the kinetics of the proliferative response of macrophages in this system are dependent upon the concentration and the time of addition of the soluble mediator. Influences that operate to limit proliferation in this system appear to be high macrophage density, the production of prostaglandin by macrophages, and other mediators present in the lymphokine preparation, such as MIF. We have tentatively termed the active soluble mediator macrophage mitogenic factor (MMF); however, its similarity to a fibroblast-produced macrophage growth factor (MGF) might indicate that, like the interferons, a term like Type II MGF would also be appropriate. The biology of this soluble mediator would appear relevant in terms of the marked proliferation and activation of macrophages known to occur during states of intense T lymphocyte-mediated immunity, as occurs during infection with facultative intracellular bacterial pathogens.