Abstract
Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3− NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.
Highlights
More than 70% of acute hepatitis C virus (HCV) infections become persistent and lead to chronic hepatitis [1, 2]
Different degrees of NKG2D expression induced by different HCV genotypes were noticed on CD56+CD3+ lymphocytes or on CD8+ T cells, but not on natural killer (NK) cells
Since HCV genotype 1 infection is more difficult to eradicate with interferon-based therapies than genotype 2, we further investigated whether CD56+CD3+ lymphocytes bearing different NKG2D expressing levels influenced the treatment effect of PEG-IFN/ ribavirin therapy
Summary
The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon
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