Gamma-interferon induction in human lymphoblasts compared with fresh mononuclear leucocytes: earlier synthesis, rapid shut-off and enhancement of yields by metabolic inhibitors.

The mechanisms of gamma-interferon (IFN-gamma) induction in fresh human peripheral blood mononuclear leucocytes (PBML) and proliferating lymphoblasts were compared. Cotreatment with mitogen (Staphylococcal enterotoxin A) and tumour promoter (mezerein) was used to induce maximum IFN-gamma production and thus to study the induction process under optimum conditions. Total IFN yields were about the same from both cell types. Proliferating lymphocytes produced IFN much earlier and more transiently than fresh PBML. Experiments with actinomycin D indicated that de novo synthesis of RNA was required for IFN-gamma production in both PBML and lymphoblasts, but that for maximal IFN-gamma production, lymphoblasts required RNA synthesis for a shorter period (1 hr) after induction than did fresh PBML (greater than 15 hr). Appropriate schedules of treatment with metabolic inhibitors actually increased IFN production in lymphoblasts. This 'superinduction' could not be demonstrated for fresh PBML, implying differences in the turn-off of IFN-gamma production in these two cell types. Taken together, these results indicate that IFN-gamma expression is regulated differently in quiescent and activated lymphocytes.