Cargando…

TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B

The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4(−)CD8(−) T (double-negative T; DNT) cells including TCRαβ(+) DNT (αβ DNT) and TCRγδ(+) DNT...

Descripción completa

Detalles Bibliográficos
Autores principales: Lai, Qintao, Ma, Shiwu, Ge, Jun, Huang, Zuxiong, Huang, Xuan, Jiang, Xiaotao, Li, Yongyin, Zhang, Mingxia, Zhang, Xiaoyong, Sun, Jian, Abbott, William G. H., Hou, Jinlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925121/
https://www.ncbi.nlm.nih.gov/pubmed/24551107
http://dx.doi.org/10.1371/journal.pone.0088475
_version_ 1782303813454004224
author Lai, Qintao
Ma, Shiwu
Ge, Jun
Huang, Zuxiong
Huang, Xuan
Jiang, Xiaotao
Li, Yongyin
Zhang, Mingxia
Zhang, Xiaoyong
Sun, Jian
Abbott, William G. H.
Hou, Jinlin
author_facet Lai, Qintao
Ma, Shiwu
Ge, Jun
Huang, Zuxiong
Huang, Xuan
Jiang, Xiaotao
Li, Yongyin
Zhang, Mingxia
Zhang, Xiaoyong
Sun, Jian
Abbott, William G. H.
Hou, Jinlin
author_sort Lai, Qintao
collection PubMed
description The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4(−)CD8(−) T (double-negative T; DNT) cells including TCRαβ(+) DNT (αβ DNT) and TCRγδ(+) DNT (γδ DNT) cells. Frequencies of circulating DNT cell subsets were measured by flow cytometry in a retrospective cohort of 51 telbivudine-treated HBeAg-positive CHB patients, 25 immune tolerant carriers (IT), 33 inactive carriers (IC), and 37 healthy controls (HC). We found that γδ DNT cell frequencies did not significantly change during treatment, being lower at baseline (P = 0.019) in patients with HBeAg seroconversion after 52 weeks of antiviral therapy (n = 20) than in those without (n = 31), and higher in the total CHB and IT than IC and HC groups (P<0.001). αβ DNT cell frequencies were similar for all groups. In vitro, γδ DNT cells suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in TCRαβ(+)CD8(+) T cells, which may require cell–cell contact, and could be partially reversed by anti-NKG2A. These findings suggest that γδ DNT cells limit CD8(+) T cell response to HBV, and may impede HBeAg seroconversion in CHB.
format Online
Article
Text
id pubmed-3925121
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39251212014-02-18 TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B Lai, Qintao Ma, Shiwu Ge, Jun Huang, Zuxiong Huang, Xuan Jiang, Xiaotao Li, Yongyin Zhang, Mingxia Zhang, Xiaoyong Sun, Jian Abbott, William G. H. Hou, Jinlin PLoS One Research Article The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4(−)CD8(−) T (double-negative T; DNT) cells including TCRαβ(+) DNT (αβ DNT) and TCRγδ(+) DNT (γδ DNT) cells. Frequencies of circulating DNT cell subsets were measured by flow cytometry in a retrospective cohort of 51 telbivudine-treated HBeAg-positive CHB patients, 25 immune tolerant carriers (IT), 33 inactive carriers (IC), and 37 healthy controls (HC). We found that γδ DNT cell frequencies did not significantly change during treatment, being lower at baseline (P = 0.019) in patients with HBeAg seroconversion after 52 weeks of antiviral therapy (n = 20) than in those without (n = 31), and higher in the total CHB and IT than IC and HC groups (P<0.001). αβ DNT cell frequencies were similar for all groups. In vitro, γδ DNT cells suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in TCRαβ(+)CD8(+) T cells, which may require cell–cell contact, and could be partially reversed by anti-NKG2A. These findings suggest that γδ DNT cells limit CD8(+) T cell response to HBV, and may impede HBeAg seroconversion in CHB. Public Library of Science 2014-02-14 /pmc/articles/PMC3925121/ /pubmed/24551107 http://dx.doi.org/10.1371/journal.pone.0088475 Text en © 2014 Lai et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Lai, Qintao
Ma, Shiwu
Ge, Jun
Huang, Zuxiong
Huang, Xuan
Jiang, Xiaotao
Li, Yongyin
Zhang, Mingxia
Zhang, Xiaoyong
Sun, Jian
Abbott, William G. H.
Hou, Jinlin
TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title_full TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title_fullStr TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title_full_unstemmed TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title_short TCRγδ(+)CD4(−)CD8(−) T Cells Suppress the CD8(+) T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B
title_sort tcrγδ(+)cd4(−)cd8(−) t cells suppress the cd8(+) t-cell response to hepatitis b virus peptides, and are associated with viral control in chronic hepatitis b
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925121/
https://www.ncbi.nlm.nih.gov/pubmed/24551107
http://dx.doi.org/10.1371/journal.pone.0088475
work_keys_str_mv AT laiqintao tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT mashiwu tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT gejun tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT huangzuxiong tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT huangxuan tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT jiangxiaotao tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT liyongyin tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT zhangmingxia tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT zhangxiaoyong tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT sunjian tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT abbottwilliamgh tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb
AT houjinlin tcrgdcd4cd8tcellssuppressthecd8tcellresponsetohepatitisbviruspeptidesandareassociatedwithviralcontrolinchronichepatitisb