The production of immunoregulatory factors by a human macrophage-like cell line. I. Characterization of an inhibitor of lymphocyte DNA synthesis.

Stimulation of the human histiocytic lymphoma, U937, with the lectins concanavalin A or phytohemagglutinin, results in the production of an inhibitor of mitogen-induced peripheral blood lymphocyte proliferation. This inhibitor of DNA synthesis (IDS) has an apparent molecular weight of approximately 65,000, is heat (56 degrees C) and acid (pH 2.0) labile, but is resistant to 10(-4) M 2-mercaptoethanol treatment. The mechanism of action is nontoxic and reversible within 24 hr of removal of the cells from IDS-containing supernatants. A variety of lymphoid and lymphoblastoid cell lines of B and T lymphocyte origin are sensitive to the effects of IDS. In contrast, the nonlymphoid cell lines HeLa, L929, MCF-7, and T47-D are unaffected by exposures to high concentrations of IDS preparations. The relationship of the IDS to other macrophage-derived inhibitory factors is discussed.