Human gamma interferon enhances release from phytohemagglutinin-stimulated T4+ lymphocytes of activities that stimulate colony formation by granulocyte-macrophage, erythroid, and multipotential progenitor cells

Human gamma interferon (HuIFNγ) was evaluated for its effects on the release from human peripheral blood T lymphocytes (>98% pure) stimulated by phytohemagglutinin (PHA) of activities that can stimulate granolocyte-macrophage (CFU-GM) colonies and clusters, erythroid (BFU-E) bursts, and mixed (CFU-GEMM) colonies. T lymphocytes did not release these activities in the absence of PHA with or without HuIFNγ. In the presence of PHA, pure natural HuIFNγ at concentrations of 0.1 to 100 U/mL significantly enhanced release of these colony-stimulating activities. Although enhanced release of granulocyte-macrophage colony-stimulating activities were noted when T lymphocytes were added to the conditioning medium in the presence of 0.1%, 0.5%, and 1% PHA, enhanced release of burst-promoting and mixed colony activities was seen only in the presence of 0.1% and 0.5% PHA. The enhanced release of colony-stimulating activities was not due to HuIFNγ-suppression of the release from PHA-stimulated T lymphocytes of suppressor molecules. The enhancing effects of natural HuIFNγ were neutralized with a monoclonal anti-natural HuIFNγ, and recombinant HuIFNγ mimicked the enhancing effects of the natural HuIFNγ. This enhancing effect was noted only when HuIFNγ was added with the T lymphocytes and PHA during the first 24 hours of incubation. T lymphocytes were separated into T4⁺, T8^-, T8⁺, and T4^- subsets (>98% pure for the appropriate phenotypes) after incubation with OKT4^- and OKT8^- monoclonal antibodies and sorting on a fluorescence-activated cell sorter (FACS). All types of colony-stimulating activities were released from each population after stimulation with PHA, but enhanced release of these activities in the presence of HuIFNγ was only detected with the T4⁺ or T8^- subsets of lymphocytes. It cannot be concluded from these studies whether HuIFNγ is enhancing the release of one or several types of colony-stimulating activities, but these studies suggest a role for HuIFNγ and T4⁺ lymphocyte subsets in the regulation in vitro of the release of colony-stimulating activities.