Immunoregulation of the mixed lymphocyte reaction by macrophage-derived factors: functional and biochemical separation of enhancing and inhibitory factors.

Positive and negative immunoregulation of the mixed lymphocyte reaction (MLR) occurred through release of macrophage(MO)-derived, soluble enhancing and inhibitory factors. Macrophages, sonicated or cultured in low concentrations, produced nondialyzable, soluble factor(s) capable of enhancing the MLR; but the culture supernatant had no biologically detectable levels of Interleukin 1, Interleukin 2, or interferon. Production of enhancing supernatants was not affected by pretreatment of MO with trypsin or anti-Thy 1 antibody plus complement. In contrast, MO cultured in high concentrations yielded an inhibitory supernatant factor(s) which suppressed MLR reactivity even when MO were cultured in the presence of indomethacin. Culturing MO with proteolytic enzyme inhibitors increased the yields of the inhibitory and enhancing factors. Both factors were precipitable with ammonium sulfate and could be separated into several biologically active fractions using anion exchange chromatography.