Xu Zhen-Yu, Dai Zhong-Shang, Gong Guo-Zhong, Zhang Min
Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.
Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.
World J Gastroenterol. 2025 Jan 21;31(3):99833. doi: 10.3748/wjg.v31.i3.99833.
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 CXCR5CD8 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 CXCR5CD8 T cells and sustained serologic response (SR) in patients undergoing 48 weeks of pegylated IFN-α (peg-IFN-α) treatment for CHB.
To elucidate the relationship between CXCR5CD8 T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-α treatment for CHB.
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 × 10 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 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.
Patients with CHB exhibited significantly lower levels of circulating CXCR5CD8 T cells compared to healthy controls ( < 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 ( = -0.189, = 0.002). However, there was no significant correlation between serum IL-21 levels and CXCR5CD8 lymphocytes ( = -0.03, = 0.625) or serum ALT levels ( = 0.026, = 0.678).
The enhanced expression of CXCR5CD8 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 CXCR5CD8 T cells as immune regulators in CHB, which may inform future therapeutic strategies to optimize antiviral treatments.
C-X-C趋化因子受体5（CXCR5）阳性CD8 T细胞是一类独特的免疫亚群，具有双重作用，在持续性病毒感染中作为细胞毒性细胞发挥作用，同时促进B细胞反应。尽管其很重要，但CXCR5阳性CD8 T细胞在慢性乙型肝炎（CHB）中的具体作用，尤其是在α干扰素（IFN-α）治疗期间，尚未完全明确。本研究旨在阐明接受聚乙二醇化干扰素-α（peg-IFN-α）治疗48周的CHB患者中CXCR5阳性CD8 T细胞与持续血清学应答（SR）之间的关系。
阐明接受peg-IFN-α治疗48周的CHB患者中CXCR5阳性CD8 T细胞与持续SR之间的关系。
本研究纳入60例接受48周peg-IFN-α治疗的乙型肝炎e抗原（HBeAg）阳性CHB患者。根据至少6个月持续HBsAg阳性状态、HBeAb阴性、乙肝病毒DNA水平超过2×10拷贝/mL以及丙氨酸氨基转移酶（ALT）水平在正常上限的2至10倍等标准评估参与者的 eligibility。在基线、第12周、第24周、第48周以及24周无治疗随访期（第72周）采集血样，通过酶联免疫吸附测定（ELISA）测量血清白细胞介素（IL）-21浓度，并通过流式细胞术分析CD8 T细胞上CXCR5和程序性死亡配体1（PD-L1）的表达情况，CXCR5是一种趋化因子受体，可引导免疫细胞至特定组织，而PD-L1是一种通过抑制T细胞活性来调节免疫反应的蛋白质。
与健康对照相比，CHB患者循环CXCR5阳性CD8 T细胞水平显著降低（<0.01）。值得注意的是，与未实现持续SR（NSR）的患者相比，实现持续SR的患者中CXCR5+CD8+ T细胞显著表达。观察到CXCR5与PD-L1表达之间存在显著相关性（=-0.189，=0.002）。然而，血清IL-21水平与CXCR5阳性CD8淋巴细胞之间（=-0.03，=0.625）或血清ALT水平之间（=0.026，=0.678）均无显著相关性。
在IFN-α治疗期间实现HBeAg血清学转换的患者中CXCR5阳性CD8 T细胞表达增强，表明这些细胞在针对乙型肝炎的抗病毒免疫反应中起关键作用。本研究突出了CXCR5阳性CD8 T细胞作为CHB免疫调节因子的潜力，这可能为优化抗病毒治疗的未来治疗策略提供参考。
