Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to influenza and herpes viruses.

Abstract

Augmentation of natural killer (NK) activity by influenza A/PC and HSV-1 viruses appears to be caused by the induction of interferon (IFN) within the NK cell population itself. These viruses induced high levels of IFN production by human large granular lymphocytes (LGL) that could be readily isolated from peripheral blood by Percoll density gradients. These LGL, which have been previously shown to account for and to be highly associated with endogenous NK activity, became augmented in their lytic function during the 18-h period that IFN was induced. Non-LGL helper cells did not appear to be required in the NK-IFN system (either T cells, B cells, or monocytes). Removal of these latter cell types by treatment with OKT3 plus complement, anti-IgM plus complement, or preincubation with silica or carrageenan had no effect on the ability of LGL to respond to the viruses. Production of IFN was also detected, albeit at lower levels, from monocytes cultured for 18 h with viruses, but no cytotoxic activity was induced. On the other hand, T cells, even in the presence of monocytes, showed neither property, and longer cultures, with virus up to 4 d, still did not alter the pattern. The IFN produced by both LGL and monocytes were predominantly IFN-alpha, as assessed by neutralization assays with antisera to IFN-alpha, -beta, and -gamma. In an individual with detectable serum antibodies to influenza A/PC, however, the IFN induced in LGL appeared to be gamma, presumably because of specific recognition of the virus. These data suggest an efficient positive self-regulatory mechanism in NK cells that may be readily switched on by viruses.

Influenza A Virus Polymerase Inhibits Type I Interferon Induction by Binding to Interferon β Promoter Stimulator 1

“…These findings suggest that the importance of the viral polymerase function in the inhibition of type I IFN production cannot be ignored. Because it is known that the type I IFN production pathway is enhanced in an autocrine manner (33,(53)(54)(55), inhibitory activity of the interferon production pathway at the early phase of viral infection might be strongly reflected in the intensity of cellular antiviral responses at the late phase. Therefore, at the early phase of viral infection, at which time an insufficient amount of viral components exist in infected cells, viral polymerase activity to repress type I IFN response might play an important role in escape from host antiviral responses.…”

Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors

“…7 In addition, our data also showed that, in T celldeficient BALB /c nude mice, intratumoral treatment resulted in lethal tumor progression in all eight nude mice, further confirming the absolute T-cell requirement in this therapeutic model. IFN -, a cytokine secreted by activated T cells and natural killer cells, has multiple immunoregulatory effects on various cell types, 29 including the capacity to stimulate the activation of CTLs, 30 natural killer cells, 31 and macrophages 32,33 and to induce /enhance the expression of class II MHC antigens. 34 Through these effects, IFN -plays a central role in promoting innate and adaptive mechanisms of host defense including tumor immunity.…”

Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

“…In addition to their antiviral activities, interferons have potent immunomodulating effects (16). Interferon (IFN) has been shown to enhance phagocytic antigen processing and immune regulatory activity of macrophages (15), specific cytotoxicity of lymphocytes for target cells, and natural killer cell activity (17). The biologic activity of IFN alfa given in low doses via the oromucosal route has been examined in many species, including humans (18).…”