Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

Abstract

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. 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). C O N C L U S I O N :O u r r e s u l t s c o n f i r m p r e v i o u s 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.

A predictive model of treatment outcome in patients with chronic HCV infection using IL28B and PD-1 genotyping

“…In the present study, we examined the relationship between the previously described [25] polymorphisms of PD-1 with the treatment of HCV chronic infection. PD-1 is an inhibitory co-stimulatory molecule that has been involved in solid organ transplant rejection [34] and viral infections [35], including HCV [36,37]. Furthermore, high expression of PD-1 in CD8+ T cells may represent a mechanism of HCV persistence [23].…”

Tumor necrosis factor-alpha blockage therapy impairs hepatitis B viral clearance and enhances T-cell exhaustion in a mouse model

“…[17][18][19] HBV-specific PD-1-positive CD8-positive T cells of patients with chronic HBV infection also displayed lower levels of the interleukin (IL)-7 receptor, CD127, which was previously described in association with the exhausted phenotype. 20 However, the effects of TNF-a blockage therapy on T-cell exhaustion and the adaptive immune response in HBV infection is still uncertain.…”

The Pd-1/B7-H1-Mediated Pro-Apoptotic Activity of Dendritic Cells as a Possible Mechanism of Antigen-Specific Response Failure in Patients With Pulmonary Tuberculosis

“…Многие микроорганизмы, которые вызыва-ют хроническую инфекцию, используют PD-1/ B7-H1-опосредованный путь индукции апоптоза Т-клеток с целью выключения эффекторных им-мунных реакций хозяина [5,12,15]. При перси-стирующих инфекциях генерируются толероген-ные ДК/Мф с повышенной экспрессией B7-H1 и низкой экспрессией костимуляторных молекул CD80 и CD86.…”