A molecular mechanism of regulation for granulocyte macrophage colony stimulating factor from T lymphocytes

We have partially purified a mitogenic factor, termed colony stimulating factor, which is secreted from a human T lymphocytic cell line, and which stimulates in vitro formation of colonies of macrophages and granulocytes by human bone marrow cells. Colony stimulating factor (CSF) produced by cells grown in serum supplemented media has a molecular weight of 60,000. It easily dissociates into a low (20,000) and a high (40,000) molecular weight component. The low molecular weight component, F I, initiates colony formation by a subset of the marrow cells. F II, the high molecular weight component, is inactive by itself, but reconstitution of F I with F II causes a dramatic increase in the number of target cells that form colonies. In serum-free media the T-cell line secretes only F I, which can be activated by F II. F II is only present when serum has been added to the medium, yet it is not present in the serum. Therefore, either the lymphocytes modify a component of the serum or they are stimulated to secrete F II by the serum. The molecular properties of this CSF suggest a possible mechanism of regulation of similar factors in that dissociation and reassociation may be physiologically important in determining which cell population is activated in hematopoiesis.