Boeijen Lauke L, Montanari Noé R, de Groen Rik A, van Oord Gertine W, van der Heide-Mulder Marieke, de Knegt Robert J, Boonstra André
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
J Infect Dis. 2017 Nov 15;216(8):969-976. doi: 10.1093/infdis/jix425.
Mucosal-associated invariant T (MAIT) cells might play a role in control of viral replication during chronic hepatitis B (cHBV) infection, but little is known of their number, phenotype, or function in cHBV patients.
We performed flow cytometry on CD3+Vɑ7.2+CD161+ MAIT cells in blood of 55 cHBV patients. Nine patients were sampled before and on entecavir treatment. Six patients on therapy underwent a liver biopsy for flow cytometric analysis. Measurements included MAIT cell frequency, phenotype, and cytokine-producing capacity.
The MAIT cells were not deleted in blood or liver of cHBV patients compared with healthy controls, but they had higher percentages of CD38+ MAIT cells in blood, which declined on entecavir treatment. Peripheral MAIT cells of patients in the HBeAg-negative phase were least activated. Cytokine-producing MAIT cells were as frequent, but granzyme B-producing MAIT cells were more frequent upon stimulation with Escherichia coli compared with healthy controls.
We demonstrate that, in sharp contrast to hepatitis C virus and human immunodeficiency virus patients, MAIT cells isolated from HBV patients are not deleted but are more activated, which can be normalized by nucleoside analog therapy. These observations may aid in deciphering the role of MAIT cells in immune responses to HBV.
黏膜相关恒定T（MAIT）细胞可能在慢性乙型肝炎（cHBV）感染期间控制病毒复制中发挥作用，但对于cHBV患者中MAIT细胞的数量、表型或功能知之甚少。
我们对55例cHBV患者血液中的CD3+Vɑ7.2+CD161+ MAIT细胞进行了流式细胞术检测。9例患者在恩替卡韦治疗前及治疗期间进行了采样。6例接受治疗的患者进行了肝活检以进行流式细胞术分析。检测指标包括MAIT细胞频率、表型和细胞因子产生能力。
与健康对照相比，cHBV患者血液和肝脏中的MAIT细胞未被清除，但血液中CD38+ MAIT细胞百分比更高，恩替卡韦治疗后该百分比下降。HBeAg阴性期患者的外周MAIT细胞活化程度最低。与健康对照相比，细胞因子产生性MAIT细胞频率相同，但经大肠杆菌刺激后，颗粒酶B产生性MAIT细胞频率更高。
我们证明，与丙型肝炎病毒和人类免疫缺陷病毒患者形成鲜明对比的是，从HBV患者中分离出的MAIT细胞未被清除，但活化程度更高，核苷类似物治疗可使其恢复正常。这些观察结果可能有助于阐明MAIT细胞在对HBV免疫反应中的作用。
