Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.

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 per...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4428701?pdf=render
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author 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
author_facet 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
author_sort Po-sung Chu
collection DOAJ
description 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.
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spelling doaj.art-88d5174904f94edd93b05ba46834d2eb2022-12-22T01:19:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012566410.1371/journal.pone.0125664Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.Po-sung ChuHirotoshi EbinumaNobuhiro NakamotoKazuo SugiyamaShingo UsuiYuko WakayamaNobuhito TanikiAkihiro YamaguchiShunsuke ShibaYoshiyuki YamagishiTakaji WakitaToshifumi HibiHidetsugu SaitoTakanori KanaiHepatitis 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.http://europepmc.org/articles/PMC4428701?pdf=render
spellingShingle 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
Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
PLoS ONE
title Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
title_full Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
title_fullStr Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
title_full_unstemmed Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
title_short Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.
title_sort genotype associated differential nkg2d expression on cd56 cd3 lymphocytes predicts response to pegylated interferon ribavirin therapy in chronic hepatitis c
url http://europepmc.org/articles/PMC4428701?pdf=render
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