Regulatory phenotype, PD-1 and TLR3 expression in T cells and monocytes from HCV patients undergoing antiviral therapy: a randomized clinical trial

Shan-shan Su; Huan He; Ling-bo Kong; Yu-guo Zhang; Su-xian Zhao; Rong-qi Wang; Huan-wei Zheng; Dian-xing Sun; Yue-min Nan; Jun Yu

doi:10.1371/journal.pone.0093620

Regulatory phenotype, PD-1 and TLR3 expression in T cells and monocytes from HCV patients undergoing antiviral therapy: a randomized clinical trial

PLoS One. 2014 Apr 7;9(4):e93620. doi: 10.1371/journal.pone.0093620. eCollection 2014.

Authors

Affiliations

¹ Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
² Department of Infectious Disease, The Fifth Hospital of Shijiazhuang City, Shijiazhuang, China.
³ Department of Liver Disease, Bethune International Peace Hospital, Shijiazhuang, China.
⁴ Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Abstract

Background & aims: The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment.

Methods: Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4+ T-cells or CD8+ T-cells and toll-like receptor (TLR) 3 expressing CD14+ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls.

Results: Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4+ or CD8+ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14+ monocytes at baseline had a high rate of cEVR (P<0.05).

Conclusions: Low peripheral TLR3 expressing CD14+ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4+ or CD8+ T-cells.

Trial registration: Chinese Clinical Trial Registry ChiCTR10001090.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD8-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / pathology
Female
Gene Expression Regulation*
Hepacivirus*
Hepatitis C, Chronic* / blood
Hepatitis C, Chronic* / drug therapy
Hepatitis C, Chronic* / pathology
Humans
Male
Middle Aged
Monocytes / metabolism*
Monocytes / pathology
Programmed Cell Death 1 Receptor / biosynthesis*
T-Lymphocytes, Regulatory / metabolism*
T-Lymphocytes, Regulatory / pathology
Toll-Like Receptor 3 / biosynthesis*

Substances

PDCD1 protein, human
Programmed Cell Death 1 Receptor
TLR3 protein, human
Toll-Like Receptor 3

Grants and funding

This study was supported by the Key Program for Science and Technology Development of Hebei Province named Study on Prevention and Control of Viral Hepatitis (10276102D). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.