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World J Gastroenterol. Jul 28, 2008; 14(28): 4551-4557
Published online Jul 28, 2008. doi: 10.3748/wjg.14.4551
Programmed death-1 expression is associated with the disease status in hepatitis B virus infection
Pian Ye, Zhi-Hong Weng, Shu-Ling Zhang, Jian-Ao Zhang, Lei Zhao, Ji-Hua Dong, Sheng-Hua Jie, Ran Pang, Rong-Hua Wei
Pian Ye, Zhi-Hong Weng, Shu-Ling Zhang, Jian-Ao Zhang, Lei Zhao, Sheng-Hua Jie, Ran Pang, Department of Hepatology and Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Ji-Hua Dong, Centralab, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Rong-Hua Wei, Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Ye P and Weng ZH contributed equally to this work; Weng ZH, Zhang SL and Ye P designed research; Ye P performed research; Zhang SL, Dong JH and Jie SH supervised the project; Zhang JA performed ELISA; Wei RH and Pang R performed real-time PCR; Ye P and Zhao L analyzed results; Ye P wrote the paper.
Correspondence to: Shu-Ling Zhang, Department of Hepatology and Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. yp_breezy@yahoo.com.cn
Telephone: +86-27-62629209
Fax: +86-27-85756636
Received: May 19, 2008
Revised: July 16, 2008
Accepted: July 23, 2008
Published online: July 28, 2008
Abstract

AIM: To define the potential role of programmed death-1/programmed death-ligand (PD-1/PD-L) pathway in different hepatitis B virus (HBV) infection disease status; we examined the expression of PD-1 on antigen specific CD8+ T cells in peripheral blood of patients with chronic hepatitis B (CHB) and acute exacerbation of hepatitis B (AEHB) infection.

METHODS: The PD-1 level on CD8+ T lymphocytes and the number of HBV specific CD8+ T lymphocytes in patients and healthy controls (HCs) were analyzed by staining with pentameric peptide-human leukocyte antigen2 (HLA2) complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction (PCR) was used to measure the serum HBV-DNA levels.

RESULTS: The level of PD-1 expression on total CD8+ T cells in CHB patients (13.86% ± 3.38%) was significantly higher than that in AEHB patients (6.80% ± 2.19%, P < 0.01) and healthy individuals (4.63% ± 1.23%, P < 0.01). Compared to AEHB patients (0.81% ± 0.73%), lower frequency of HBV-specific CD8+ T cells was detected in chronic hepatitis B patients (0.37% ± 0.43%, P < 0.05). There was an inverse correlation between the strength of HBV-specific CD8+ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8+ T cells in CHB and AEHB subjects (R = 0.541, P < 0.01). However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase (ALT) levels (R = 0.066, P > 0.05).

CONCLUSION: Our results confirm previous reports that HBV specific CD8+ T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B with persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8+ T cell response.

Keywords: Chronic hepatitis B; Acute exacerbation of hepatitis B; Programmed death-1; Programmed death-ligand 1; Pentamer; Serum viral load; Blockade