Effects of recombinant and hybrid recombinant human leukocyte interferons on cytotoxic activity of natural killer cells.

Abstract

Two recombinant human leukocyte interferons (A and D), five hybrid interferons containing varying portions of A and D, and one fibroblast recombinant interferon were tested over a wide range of concentrations for their ability to modulate cytolytic activity of human natural killer (NK) cells. All of the interferons tested were purified to homogeneity. Although all the interferons were active, there were significant quantitative differences in their ability to augment cytolysis and the rank order of potency was reproducible among donors. The various recombinant interferons were also tested for their ability to augment mouse NK activity and the parental D and the A/D hybrids exhibited significant augmentation of cytolysis, which was consistent with their interspecies reactivity in viral neutralization assays. There generally was a direct correlation between antiviral activity and the ability of interferon to augment mouse NK activity; however, this correlation was not evident when tested on human cells. The study of these hybrids led to the identification of two molecules (A/D Bgl and A/D Pvu) which are very active in augmenting mouse NK activity. In addition, considerable insight has been obtained regarding the structure-function relationship of these leukocyte interferons and their ability to boost murine NK. This biological activity was associated with the COOH-terminal portion of the D interferon.