Restored Circulating Invariant NKT Cells Are Associated with Viral Control in Patients with Chronic Hepatitis B
Restored Circulating Invariant NKT Cells Are Associated with Viral Control in Patients with Chronic Hepatitis B
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恢复循环不变 NKT 细胞与慢性乙型肝炎患者的病毒控制相关
DOI：
10.1371/journal.pone.0028871
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发表时间：
2011-12-16
期刊：
影响因子：
3.7
通讯作者：
Hou, Jinlin
中科院分区：
文献类型：
--
作者：
Jiang, Xiaotao;Zhang, Mingxia;Hou, Jinlin
不变NKT（iNKT）细胞参与多种感染性疾病的发病机制。然而，它们在B型肝炎病毒（HBV）感染中的作用尚未完全了解，特别是在人类物种中。采用流式细胞术检测35例慢性B型肝炎（CH B）患者、25例非活动性携带者（IC）和36例健康对照者（HC）外周血单个核细胞（PBMC）中iNKT细胞的比例。对19例接受替比夫定抗病毒治疗的CHB患者进行了纵向分析。此后，通过细胞因子分泌和双室技术评价iNKT细胞的免疫功能。CHB患者外周血iNKT细胞的中位频率（0.13%）低于HC（0.24%，P = 0.01）和IC（0.19%，P = 0.02），在替比夫定抗病毒治疗期间显著升高（P = 0.0176）。 CHB患者iNKT细胞上CC趋化因子受体5（CCR5）和CCR6的表达（分别为82.83% ± 9.87%，67.67% ± 16.83%）明显高于常规T细胞（30.5% ± 5.65%，14.02% ± 5.92%，P均<0.001）。此外，iNKT细胞可以向CC趋化因子配体5迁移。基线时CD4 −/CD4 + iNKT细胞比值高（≥ 1.0）的患者HBeAg血清转换率（58.33%）高于比值低的患者（<1.0，0%，P = 0.0174）。 总之，CHB患者外周iNKT细胞的频率较低，在病毒控制下增加至正常水平。在接受替比夫定治疗的CHB患者中，基线时CD4 −/CD4 + iNKT细胞的比值可能是HBeAg血清转换的有用预测因子。
Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4−/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4−/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy.