ISSN:
1573-2592
Keywords:
Hepatitis C virus
;
cytotoxic T lymphocytes
;
transforming growth factor-β1
;
interleukin-10
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract In hepatitis C virus (HCV) infection, TGF-β1 is upregulated in the liver and may be involved in the pathogenesis of chronic liver disease. TGF-β1 is also produced by activated T cells and acts as a potent immunosuppressor. The aim of this study was to investigate the roles of TGF-β1 in HCV-specific cytotoxic T lymphocyte (CTL) induction and enhance their killer activity by TGF-β1 modulation. We generated anti-HCV CTL from peripheral blood mononuclear cells from HLA-A2 patients under stimulation with the HCV-core peptide having the HLA-A2.1 binding motif. The lytic activities of CTL or precursor frequency (CTLpf) generated with or without anti-TGF-p antibody were compared. To optimize the IL-2 dose for CTL induction, low (50 U/ml) and high (500 U/ml) doses were tested and the lytic activities were compared. TGF-β1 amounts in the supernatants were assessed by enzyme-linked immunosorbent assay and by their growth inhibitory effect on mink lung epithelial cells. CTL activity was enhanced by anti-TGF-β antibody in a dose-dependent manner but CTLpf did not significantly change. A high dose of IL-2 reduced the activity to 45% of that observed with a low dose, whereas TGF-β1 increased as the dose of IL-2 increased. Exogenous IL-10 reversed the inhibitory effect of a high dose of IL-2 on the killing activity by reducing TGF-β1 mRNA expression in T cells and its production. These results demonstrated that endogenous TGF-β1 is an autocrine suppressor in CTL induction in vitro. Therefore, the blockade of endogenous TGF-β1 could enhance the killing potential of anti-HCV CTL.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1027367626317
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