Human gamma interferon enhances release from phytohemagglutinin- stimulated
T4+ lymphocytes of activities that stimulate colony formation by
granulocyte-macrophage, erythroid, and multipotential progenitor cells
W Piacibello, L Lu, D Williams, M Aglietta, BY Rubin, S Cooper, M Wachter, F Gavosto and HE Broxmeyer
Human gamma interferon (HuIFN gamma) was evaluated for its effects on the
release from human peripheral blood T lymphocytes (greater than 98% pure)
stimulated by phytohemagglutinin (PHA) of activities that can stimulate
granulocyte-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 HuIFN gamma. In the
presence of PHA, pure natural HuIFN gamma 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 HuIFN gamma-suppression of the release from PHA-stimulated T
lymphocytes of suppressor molecules. The enhancing effects of natural HuIFN
gamma were neutralized with a monoclonal anti-natural HuIFN gamma, and
recombinant HuIFN gamma mimicked the enhancing effects of the natural HuIFN
gamma. This enhancing effect was noted only when HuIFN gamma 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 (greater
than 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 HuIFN gamma was only
detected with the T4+ or T8- subsets of lymphocytes. It cannot be concluded
from these studies whether HuIFN gamma is enhancing the release of one or
several types of colony-stimulating activities, but these studies suggest a
role for HuIFN gamma and T4+ lymphocyte subsets in the regulation in vitro
of the release of colony-stimulating activities.
Volume 68,
Issue 6,
pp. 1339-1347,
12/01/1986
Copyright © 1986 by The American Society of Hematology
