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


BACKGROUND
Chinese Clinical Trial Registry ChiCTR10001090.
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Shan-shan
SS
Su
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Huan
H
He
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Ling-bo
LB
Kong
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Yu-guo
YG
Zhang
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Su-xian
SX
Zhao
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Rong-qi
RQ
Wang
Department of Infectious Disease, The Fifth Hospital of Shijiazhuang City, Shijiazhuang, China.
Huan-wei
HW
Zheng
Department of Liver Disease, Bethune International Peace Hospital, Shijiazhuang, China.
Dian-xing
DX
Sun
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Yue-min
YM
Nan
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.
Jun
J
Yu
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000473:pathology; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*
C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3