T-bet expression in CD8+ T cells associated with chronic hepatitis B virus infection
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RESEARCH
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T-bet expression in CD8+ T cells associated with chronic hepatitis B virus infection Rongshan Fan1, Yinghua Lan1, Jiwang Chen2, Yanxin Huang1, Qin Yan1, Lisheng Jiang1, Shupeng Song1 and Yongguo Li1*
Abstract Background: The mechanisms leading to virus-specific CD8+ T cell dysfuction in chronic hepatitis B virus (HBV) infection remain to be elucidated. Our study focused on the role of transcription factor T-bet in HBV infection because it is a crucial regulator of T cell immunity. Methods: We assessed the expression of T-bet along with PD-1, IFN-γ and perforin, in HBV-specific CD8+ T cells from resolved acute hepatitis B (rAHB) patients, chronic hepatitis B (CHB) patients, as well as asymptomatic HBV carriers (ASCs). We observed dynamic changes of T-bet, PD-1, IFN-γ and perforin in acute stage and recovery stage of acute hepatitis B (AHB). Results: Comparing with other cohorts, HBV-specific CD8+ T cells from rAHB demonstrated a superior ability in T-bet, IFN-γ and perforin expression, but an inferior ability in PD-1 expression. In the CHB group, the level of T-bet has a linear relationship with the level of PD-1, IFN-γ and HBV DNA, respectively. A lower expression of T-bet and PD-1 was observed in ASCs when compared with CHB. A higher expression of T-bet, PD-1, IFN-r and perforin was observed in acute stage when compared with the recovery stage of AHB. Conclusions: Our results suggest that expression of T-bet may influence the function of HBV-specific CD8+ T cells and thus can be an attractive target for modulation to improve HBV-specific immunity in CHB. Keywords: T-bet transcription factor, Hepatitis B virus, CD8 positive T lymphocytes
Background Both the quantity and quality of the adaptive antiviral immune response influence the clinical outcome of HBV infection [1]. A multi-specific and vigorous T cell response is present in acute hepatitis B (AHB) patients who have successfully cleared HBV infection. However, in chronic HBV infection including CHB and ASCs, the T cell immune responses are weak and oligoclonal [2]. HBV-specific CD8+ T cells play important roles in clearance of HBV infection and in the control of HBV replication [3]. A sustained and potent CD8+ T cell response to HBV antigen is associated with resolved acute HBV infection, but not with chronic HBV infection [4]. Chronic HBV infection acquired perinatally or in early childhood is believed to progress through distinct * Correspondence: [email protected] 1 Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Post Street 23rd, Nangang District, Harbin 150001, People’s Republic of China Full list of author information is available at the end of the article
phases: immune tolerant, immune active and inactive carrier. ASC means a patient is in immune tolerant phase, while CHB means a patient is in immune active phase [5]. The constant existence of viral antigens intrinsic in chronic infection may lead to loss of function in antigen-specific T cells, decreased production of inter
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