Human gamma interferon strongly upregulates its own gene expression in peripheral blood lymphocytes.
The product of the human IFN-gamma gene was found to be a powerful upregulatory stimulus for its own gene expression in lectin-activated human PBMC. The INF-gamma autosuperinduction response was further enhanced by "priming" PBMC with IFN-gamma. Primed cells maximally upregulated their levels of IFN-gamma 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-gamma 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-gamma on producer cells is still unclear. These results may be important both to an understanding of the pathogenesis of immune dysfunction and to the design of more effective immunotherapy.
Hardy
K J
KJ
Howard Hughes Medical Institute, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Sawada
T
T
D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D007371:Interferon-gamma