Evidence for suppressor T-cell regulation of human gamma interferon production

Human gamma interferon (IFN gamma) production by peripheral blood lymphocytes (PBL) appears to be regulated by a dynamic interaction between distinct regulatory T-cell subsets and IFN gamma-producing cells. Time-course kinetics of IFN gamma production in response to T-cell mitogens suggested that suppressor cells were being activated to control IFN gamma production at 6 to 8 days of culture. This was confirmed by cocultivation of preactivated (4 to 6 days with mitogen) suppressor cells and fresh lymphocytes with a resultant depressed IFN gamma response to stimulation with staphylococcal enterotoxin A. The appearance of suppressor cells in cultures preceded the decline in IFN gamma production, which is consistent with suppressor cell regulation of IFN gamma production. The suppressor cells were of the phenotype Leu 2+,3- as determined by "panning" with monoclonal antibodies. This phenotype corresponds to that reported for suppressor cells of the autologous mixed-lymphocyte reaction and for antibody production. Abrogation of suppressor cell activity by addition of interleukin 2 (IL 2) to cultures and the absorption of IL 2 from cultures by suppressor cells suggested that suppressor cells regulated IFN gamma production by sequestering IL 2 that is required for IFN gamma production. IFN gamma production by human PBL thus appears to be regulated by an interaction between IL 2 (from helper cells), suppressor cells (absorption of IL 2), and IFN gamma-producing cells.