Twenty-four subjects with chronic HCV infection were treated with IFN for six months. Liver biopsies were obtained before and after therapy. The number of mononuclear cells staining for CD3, CD4, CD8, 3G8, and the number of mononuclear... more
Twenty-four subjects with chronic HCV infection were treated with IFN for six months. Liver biopsies were obtained before and after therapy. The number of mononuclear cells staining for CD3, CD4, CD8, 3G8, and the number of mononuclear cells, liver cells, and bile duct cells staining for class I and II MHC antigens in the biopsies was determined. NK cells increased from 16±3 to 28±3 cells per 5 high-power fields (HFP) (P≤0.03). The number of bile duct cells expressing class I and II MHC Ag and liver cells expressing class II MHC Ag increased (allP≤0.03). The only parameter that distinguished responders from nonresponders was the number of NK cells. Following IFN withdrawal, expression of these antigens declined. Based upon these data, it is concluded that IFN treatment of HCV increases: (1) the NK cells number; (2) the expression of class I MHC Ag on bile duct cells and the expression of class II MHC Ag on liver and bile duct cells; and (3) with IFN withdrawal, these changes disappear.
In contrast to the large number of class I and II cytokine receptors, only four Janus kinase (Jak) proteins are expressed in mammalian cells, implying the shared use of these kinases by many different receptor complexes. Consequently, if... more
In contrast to the large number of class I and II cytokine receptors, only four Janus kinase (Jak) proteins are expressed in mammalian cells, implying the shared use of these kinases by many different receptor complexes. Consequently, if receptor numbers exceed the amount of available Jak, cross-interference patterns can be expected. We have engineered two model cellular systems expressing two different exogenous Tyk2-interacting receptors. A receptor chimera was generated wherein the extracellular part of the interferon type 1 receptor (Ifnar1) component of the interferon-α/β receptor is replaced by the equivalent domain of the erythropoietin receptor. Despite Tyk2 activation, erythropoietin treatment of cells expressing this erythropoietin receptor/Ifnar1 chimera did not evoke any detectable IFN-type response. However, a dose-dependent interference with signal transduction via the endogenous Ifnar complex was found for STAT1, STAT2, STAT3, Tyk2, and Jak1 activation, for gene induc...
