TY - JOUR
T1 - Genotype-associated differential NKG2D expression on CD56+CD3+ lymphocytes predicts response to pegylated-interferon/ribavirin therapy in chronic hepatitis C
AU - Chu, Po Sung
AU - Ebinuma, Hirotoshi
AU - Nakamoto, Nobuhiro
AU - Sugiyama, Kazuo
AU - Usui, Shingo
AU - Wakayama, Yuko
AU - Taniki, Nobuhito
AU - Yamaguchi, Akihiro
AU - Shiba, Shunsuke
AU - Yamagishi, Yoshiyuki
AU - Wakita, Takaji
AU - Hibi, Toshifumi
AU - Saito, Hidetsugu
AU - Kanai, Takanori
N1 - Publisher Copyright:
© 2015 Chu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/5/12
Y1 - 2015/5/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930647567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930647567&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0125664
DO - 10.1371/journal.pone.0125664
M3 - Article
C2 - 25965701
AN - SCOPUS:84930647567
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 5
M1 - e0125664
ER -
