Expression levels of CD28, CTLA‑4, PD‑1 and Tim‑3 as novel indicators of T‑cell immune function in patients with chronic hepatitis B virus infection

Wang,Lin; Zhao,Chunnan; Peng,Qunxin; Shi,Jinfang; Gu,Guohao

doi:10.3892/br.2014.217

Expression levels of CD28, CTLA‑4, PD‑1 and Tim‑3 as novel indicators of T‑cell immune function in patients with chronic hepatitis B virus infection

Authors:
- Lin Wang
- Chunnan Zhao
- Qunxin Peng
- Jinfang Shi
- Guohao Gu
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Affiliations: Department of Laboratory Medicine, Key Laboratory of Clinical Immunology of Jiangsu Province, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: January 7, 2014 https://doi.org/10.3892/br.2014.217
Pages: 270-274

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Abstract

Chronic hepatitis B (CHB) is one of the most common types of infectious diseases worldwide. The interaction between hepatitis B virus (HBV) and the host immune response is vital for the clinical outcome of HBV infection. Costimulatory signals are key factors for the host immune response and play a critical role in innate immunity, particularly antiviral immunity. The aim of the present study was to investigate the correlation between the expression levels of costimulatory molecules and the different states of CHB infection, including the expression levels prior to and following treatment with antiviral agents. The expression levels of CD28, CTLA‑4, PD‑1, Tim‑3 and T‑cell subsets were determined by flow cytometry. The load of HBV DNA in the serum was detected by quantitative polymerase chain reaction and the serology markers, including HBeAg and alanine aminotransferase (ALT), were measured by conventional methods. Compared to the healthy control group, the expression levels of CD28 and CTLA‑4 on CD4 T cells prior to and following treatment with antiviral agents (the pre‑ and post‑treatment groups, respectively) were significantly decreased, while the expression levels of Tim‑3 on CD4 and CD8 T cells were significantly increased. In addition, the expression levels of PD‑1 on CD4 and CD8 T cells in the pre‑treatment group were significantly increased compared to those in the post‑treatment and healthy control groups. Moreover, the multivariate analysis revealed that the levels of ALT and HBV‑DNA in the serum were significantly positively correlated with PD‑1 expression levels. In conclusion, the expression levels of these costimulatory molecules reflect the immune dysfunction of T cells in patients with CHB and, combined with T‑cell subset analysis may be used as a novel evaluation system of immune function in patients with HBV infection.

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