Interleukin-21 Responses in Patients with Chronic Hepatitis B
Interleukin-21 Responses in Patients with Chronic Hepatitis B
复制标题
慢性乙型肝炎患者的白细胞介素 21 反应
DOI：
10.1089/jir.2013.0119
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发表时间：
2015-02-01
影响因子：
2.3
通讯作者：
Qin, Chengyong
中科院分区：
文献类型：
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作者：
Li, Jie;Ren, Wanhua;Qin, Chengyong
白细胞介素（IL）-21已被证明在控制慢性病毒感染中发挥关键作用。然而，IL-21在慢性B型肝炎（CH B）发病过程中对T细胞免疫的调节作用尚不清楚。本研究检测了77例不同程度慢性乙型肝炎（CHB）患者免疫清除期（IC）、25例B肝炎病毒（HBV）感染者免疫耐受期（IT）和25例健康对照者（HC）血清IL-21水平，并探讨其与主要临床指标的关系。在存在或不存在抗IL-21抗体或重组IL-21的情况下，用B核心抗原（HBcAg）刺激CH B患者的外周血单个核细胞，并通过流式细胞术表征HBcAg特异性IL-21（+）CD 4（+）和干扰素（IFN）-γ（+）CD 8（+）T细胞的频率。结果表明，IC型CHB患者血清IL-21水平明显高于其他各组，且与血清HBV DNA、HBeAg水平呈正相关。IC CHB患者中HBcAg特异性IL-21（+）CD 4（+）T细胞的频率较低。此外，IL-21增强HBcAg特异性IFN-γ（+）CD 8（+）T细胞增殖，而用抗IL-21处理抑制抗原特异性IFN-γ（+）CD 8（+）T细胞体外扩增。我们的研究结果表明，在人类慢性HBV感染过程中，IL-21积极调节促炎性IFN-γ（+）CD 8（+）T细胞反应。
Interleukin (IL)-21 has been demonstrated to play a pivotal role in controlling chronic viral infections. However, little is known about the regulatory role of IL-21 in T cell immunity during the process of chronic hepatitis B (CHB). In the present study, the levels of serum IL-21 in 77 patients with various degrees of CHB in immune clearance phase (IC), 25 patients infected with hepatitis B virus (HBV) in immune tolerance phase (IT), and 25 healthy controls (HC) were measured and their potential association with major clinic indexes was examined. Peripheral blood mononuclear cells from CHB patients were stimulated with hepatitis B core antigen (HBcAg) in the presence or absence of anti-IL-21 antibody or recombinant IL-21, and the frequency of HBcAg-specific IL-21(+)CD4(+) and interferon (IFN)-gamma(+)CD8(+) T cells was characterized by flow cytometry. Our data indicated that the levels of serum IL-21 were significantly higher in the IC CHB patients than that in the other groups and were positively correlated with the levels of serum HBV DNA and HBeAg in the IC patients. There was a low frequency of HBcAg-specific IL-21(+)CD4(+) T cells in IC CHB patients. Further, IL-21 enhanced HBcAg-specific IFN-gamma(+)CD8(+) T cell proliferation, while treatment with anti-IL-21 inhibited antigen-specific IFN-gamma(+)CD8(+) T cell expansion in vitro. Our findings imply that IL-21 positively regulates proinflammatory IFN-gamma(+)CD8(+) T cell responses during the process of chronic HBV infection in humans.