Xu ZY, Dai ZS, Gong GZ, Zhang M. C-X-C chemokine receptor type 5+CD8+ T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferon-alpha treatment. World J Gastroenterol 2025; 31(3): 99833 [PMID: 39839901 DOI: 10.3748/wjg.v31.i3.99833]
Corresponding Author of This Article
Min Zhang, MD, Doctor, Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road Central, Changsha 410011, Hunan Province, China. zhangmin001@csu.edu.cn
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Infectious Diseases
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Clinical Trials Study
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Xu ZY, Dai ZS, Gong GZ, Zhang M. C-X-C chemokine receptor type 5+CD8+ T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferon-alpha treatment. World J Gastroenterol 2025; 31(3): 99833 [PMID: 39839901 DOI: 10.3748/wjg.v31.i3.99833]
World J Gastroenterol. Jan 21, 2025; 31(3): 99833 Published online Jan 21, 2025. doi: 10.3748/wjg.v31.i3.99833
C-X-C chemokine receptor type 5+CD8+ T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferon-alpha treatment
Zhen-Yu Xu, Zhong-Shang Dai, Guo-Zhong Gong, Min Zhang
Zhen-Yu Xu, Zhong-Shang Dai, Guo-Zhong Gong, Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Min Zhang, Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Co-first authors: Zhen-Yu Xu and Zhong-Shang Dai.
Author contributions: Xu ZY and Dai ZS collected data, drafted the manuscript, and critically revised the manuscript; Zhang M supervised the study; Gong GZ designed the study and revised the manuscript. All authors approved the final version of the manuscript. Xu ZY and Dai ZS contributed equally to this work as co-first authors.
Supported by Changsha Science and Technology Program, No. kq2022397; Natural Science Foundation of Hunan Province (Departmental Joint Fund), No. 2023JJ60440; Research Program of Health Commission of Hunan Province, No. 202303088786; Clinical Medical Research Center for Viral Hepatitis of Hunan Province, No. 2023SK4009; and the Scientific Research Program of FuRong Laboratory, No. 2023SK2108.
Institutional review board statement: The research was approved by the Ethics Committee of the Second Xiangya Hospital.
Clinical trial registration statement: This trial was registered at http://clinicaltrials.gov as (NCT01760122) on 03-01-2013.
Informed consent statement: All study participants or their legal guardian provided informed written consent regarding personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors disclose no conflicts.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Corresponding author: Min Zhang, MD, Doctor, Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road Central, Changsha 410011, Hunan Province, China. zhangmin001@csu.edu.cn
Received: July 31, 2024 Revised: October 30, 2024 Accepted: November 15, 2024 Published online: January 21, 2025 Processing time: 141 Days and 17.1 Hours
Abstract
BACKGROUND
C-X-C chemokine receptor type 5 (CXCR5)+CD8+ T cells represent a unique immune subset with dual roles, functioning as cytotoxic cells in persistent viral infections while promoting B cell responses. Despite their importance, the specific role of CXCR5+CD8+ T cells in chronic hepatitis B (CHB), particularly during interferon-alpha (IFN-α) treatment, is not fully understood. This study aims to elucidate the relationship between CXCR5+CD8+ T cells and sustained serologic response (SR) in patients undergoing 48 weeks of pegylated IFN-α (peg-IFN-α) treatment for CHB.
AIM
To elucidate the relationship between CXCR5+CD8+ T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-α treatment for CHB.
METHODS
This study enrolled 60 patients with hepatitis Be antigen (HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α treatment. Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months, HBeAb-negative, hepatitis B virus DNA levels exceeding 2 × 104 copies/mL, and alanine aminotransferase (ALT) levels between 2 and 10 times the upper limit of normal. Blood samples were collected at baseline and at weeks 12, 24, 48, and a 24-week treatment-free follow-up (week 72) to measure serum interleukin (IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1 (PD-L1) expression on CD8+ T cells by flow cytometry, CXCR5 is a chemokine receptor that directs immune cells to specific tissues, while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.
RESULTS
Patients with CHB exhibited significantly lower levels of circulating CXCR5+CD8+ T cells compared to healthy controls (P < 0.01). Notably, CXCR5+CD8+ T cells were prominently expressed in patients who achieved sustained SR compared to non-SR (NSR). A significant correlation was observed between CXCR5 and PD-L1 expression (r = -0.189, P = 0.002). However, there was no significant correlation between serum IL-21 levels and CXCR5+CD8+ lymphocytes (r = -0.03, P = 0.625) or serum ALT levels (r = 0.026, P = 0.678).
CONCLUSION
The enhanced expression of CXCR5+CD8+ T cells in patients achieving HBeAg seroconversion during IFN-α treatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B. This study highlights the potential of CXCR5+CD8+ T cells as immune regulators in CHB, which may inform future therapeutic strategies to optimize antiviral treatments.
Core Tip: This study highlights the pivotal role of C-X-C chemokine receptor type 5 (CXCR5)+CD8+ T cells in chronic hepatitis B (CHB) during pegylated interferon-alpha treatment. Our findings revealed that patients who achieved sustained serologic response exhibited higher baseline and treatment levels of CXCR5+CD8+ T cells, suggesting a connection between CXCR5 expression and IFN-induced antiviral immune responses. This research emphasizes the importance of CXCR5+CD8+ T cells as a potential biomarker for monitoring treatment efficacy in CHB patients.
