Human γ interferon strongly upregulates its own gene expression in peripheral blood lymphocytes

Abstract

The product of the human IFN-γ gene was found to be a powerful upregulatory stimulus of its own gene expression in lectin-activated human PBMC. The INF-γ autosuperinduction response was further enhanced by 'priming' PBMC with IFN-γ. Primed cells maximally upregulated their levels of IFN-γ specific mRNA 4-fold faster and more than 20-fold higher than mock-stimulated cells. High mRNA levels persisted for several days after stimulation, and enhanced secretion of biologically active IFN-γ paralleled the observed upregulation of gene expression. Producer cells demonstrating this response were found to be primarily localized to the rosette E- (Leu 11+) fraction of PBMC and appear to be of the LGL/NK variety. Whether the autosuperinduction phenomenon occurs through direct or indirect effects of IFN-γ on producer cells is still unclear. These results may by important both to an understanding of the pathogenesis of immune dysfunction and to the design of more effective immunotherapy.