Genotype-associated differential NKG2D expression on CD56+CD3+ lymphocytes predicts response to pegylated-interferon/ribavirin therapy in chronic hepatitis C

Po Sung Chu, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Kazuo Sugiyama, Shingo Usui, Yuko Wakayama, Nobuhito Taniki, Akihiro Yamaguchi, Shunsuke Shiba, Yoshiyuki Yamagishi, Takaji Wakita, Toshifumi Hibi, Hidetsugu Saito, Takanori Kanai

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1 Citation (Scopus)

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. Pretreatment 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.

Original languageEnglish
Article numbere0125664
JournalPloS one
Volume10
Issue number5
DOIs
Publication statusPublished - 2015 May 12

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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