Pretreatment of human lymphocytes with interferon enhances the synthesis of interferon in cocultures with allogeneic cells.
Human lymphocytes pretreated with interferon (IFN) alpha, beta, or gamma produced 17 times more IFN alpha (600-10,000 units/ml) than nontreated lymphocytes when cocultivated with allogeneic cells. Significant increases in IFN production (500-3,000 units/ml) were observed when lymphocytes were treated with IFN for just 2 h, and peak levels (10,000 units/ml) were produced after a 4-h treatment. The amount of IFN required to show the maximum priming effect was between 100 and 1,000 units; higher levels of IFN were inhibitory. The levels of IFN increased as the lymphocyte-to-target-cell ratio increased from 2:1 to 10:1 and decreased at higher ratios. The decrease in IFN production at higher ratios of lymphocytes to target cells could not be attributed to the presence of a soluble suppressor substance. The additional IFN found in supernates was attributed to enhanced production of IFN by the same cells, rather than recruitment of more cells to produce IFN. This conclusion is based on the fact that no increase in the number of cells staining positive for IFN production was observed in primed lymphocytes. The increased amount of IFN due to priming enhanced both nonsensitized cytotoxic activity and the transfer of antiviral activity, which could be prevented by antibody to IFN. The data suggest that priming may be an important biological mechanism for obtaining significant levels of IFN more rapidly in the vicinity of transformed cells or virus-infected tissues.
D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012845:Sindbis Virus / Q000187:drug effects
D007370:Interferon Type I; D007372:Interferons