Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection
Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection
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DOI：
10.1002/hep.20649
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发表时间：
2005-04-01
期刊：
影响因子：
13.5
通讯作者：
Janssen, HLA
中科院分区：
文献类型：
--
作者：
Stoop, JN;van der Molen, RG;Janssen, HLA
慢性乙型肝炎病毒 (HBV) 感染的特点是对 HBV 的免疫反应较弱。调节性 T 细胞 (T-reg) 可以抑制效应 T 细胞的功能，因此可能是这种免疫反应受损的关键因素。 T-reg 功能或数量的变化可以解释慢性乙型肝炎患者抗病毒反应的降低。为了研究 T-reg 在慢性 HBV 感染中的作用，我们比较了 50 名慢性 HBV 患者、23 名健康对照者和 9 名已治愈 HBV 感染者的外周血中 T-reg 的比例频率和功能。与健康对照和乙肝病毒感染已治愈的个体相比，慢性乙肝患者外周血中 CD4+ 细胞群中检测到的 T-reg（定义为 CD4、CD25、CD45RO 和细胞毒性 T 淋巴细胞相关抗原 4 阳性细胞）比例较高。因此，慢性乙型肝炎患者的 FoxP3 信使 RNA 水平高于健康对照。慢性乙型肝炎患者外周血单核细胞（PBMC）中CD25（+）细胞的耗竭导致乙型肝炎核心抗原刺激后增殖增强。用 CD4(+)CD25(+) T-reg 重建这些耗尽的 PBMC 导致 HBV 特异性增殖和干扰素 γ 产生呈剂量依赖性减少。总之，与对照组相比，慢性乙型肝炎患者外周血中 T-reg 的百分比增加。 T-reg 对 HBV 特异性 T 辅助细胞具有免疫抑制作用。 HBV 特异性 Treg 的存在可能会导致针对该病毒的免疫反应不足，从而导致慢性感染。
Chronic hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. Regulatory T cells (T-reg) can suppress the function of effector T cells and may thus be key players in this impaired immune response. Changes in the functionality or number of T-reg could explain the decreased antiviral response in chronic HBV patients. To investigate the role of T-reg in chronic HBV infection, we compared the proportional frequency and functionality of T-reg in peripheral blood of 50 chronic HBV patients, 23 healthy controls, and 9 individuals with a resolved HBV infection. A higher percentage of T-reg, defined as CD4, CD25, CD45RO, and cytotoxic T-lymphocyte-associated antigen 4-positive cells, was detected within the population of CD4(+) cells in peripheral blood of chronic HBV patients compared with healthy controls and individuals with a resolved HBV infection. Accordingly, chronic HBV patients displayed a higher FoxP3 messenger RNA level than healthy controls. Depletion of CD25(+) cells from peripheral blood mononuclear cells (PBMC) of chronic HBV patients resulted in an enhanced proliferation after stimulation with HBV core antigen. Reconstitution of these depleted PBMC with CD4(+)CD25(+) T-reg resulted in a dose-dependent reduction of both HBV-specific proliferation and interferon gamma production. In conclusion, chronic HBV patients harbor an increased percentage of T-reg in peripheral blood compared with controls. T-reg have an immunosuppressive effect on HBV-specific T helper cells. The presence of HBV-specific Treg could contribute to an inadequate immune response against the virus, leading to chronic infection.