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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |