Enhanced functions of peripheral γδ T cells in chronic hepatitis B infection during interferon α treatment in vivo and in vitro

PLoS One. 2015 Mar 16;10(3):e0120086. doi: 10.1371/journal.pone.0120086. eCollection 2015.

Abstract

Background: γδ T cells play an important role in infectious, autoimmune, or neoplastic diseases. Here, a study was conducted to investigate the dynamic changes in phenotype and function of peripheral γδ T cells in patients with chronic hepatitis B (CHB) during pegylated-interferon (pegIFN)-α treatment, and to explore their roles in IFN-α therapy.

Methods: Total 15 CHB patients with pegIFN-α therapy and 6 healthy controls (HC) were enrolled in this study. Flow cytometry was used for the study of frequency of peripheral γδ T cells, subtypes, effector or memory γδ T cells, and also the IFN-γ+, TNF-α+, CD107a+ or Granzyme B+ γδ T cells in 10 patients at week 0, 4, 8, 12, 24, 36 and 48 of treatment. Another 5 CHB patients and 6 HC were recruited for the γδ T cell isolation, and gene expression in γδ T cells was evaluated before or after IFN-α treatment in vitro.

Results: Although γδT cells decreased in CHB patients during pegIFN-α therapy, their capacities to produce TNF-α and to express CD107a were enhanced. More effector γδT cells (CD27-CD45RA+) were found in the response group than in non-response group. Furthermore, IFN-α boosted the expression of Mx2 and cytokine genes in γδT cells from CHB patients in vitro.

Conclusion: IFN-α could enhance the cytokine production or cytotoxicity potential of γδT cells in vivo and in vitro. The enhanced function of γδT cells might contribute to the effect of IFN-α treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA, Viral
  • Gene Expression
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunophenotyping
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Lymphocyte Count
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Myxovirus Resistance Proteins / metabolism
  • Phenotype
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • Cytokines
  • DNA, Viral
  • Interferon-alpha
  • Lysosomal-Associated Membrane Protein 1
  • MX2 protein, human
  • Myxovirus Resistance Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Natural Science Foundation of China (30901264), http://www.nsfc.gov.cn/, to Min Chen; the National Science and Technology Major Project of China (2012ZX1002007001, 2011ZX09302005, 2012ZX09303001-001, 2012ZX10002003), http://www.nmp.gov.cn/, to Hong Ren, and the Medical Science Foundation Project of Health Bureau of Chongqing Province (2011-2-152), http://www.cqwsjsw.gov.cn/, to Hui Peng. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.