2021年6月11日，公共实验技术中心免疫学技术平台在科技大楼13-2室举办了SCI论文报告会，硕士研究生文雪作了题目为“Mucosal-Associated Invariant T Cell Dysregulation Correlates With Conjugated Bilirubin Level in Chronic HBV Infection”的报告。会议由公共实验技术中心免疫学技术平台主任袁青教授主持，平台师生12人参加了本次会议。

报告内容主要介绍了粘膜相关不变T细胞(MAIT)是一种非常规T细胞，主要受主要组织相容性复合体I类相关蛋白1(MR1)的限制。作者发现MAIT细胞对HBV转染的肝细胞有很强的细胞毒作用，这种作用依赖于MR1。相关分析表明，MAIT细胞频率与疾病进展相关，与血清结合胆红素水平呈负相关，是高结合胆红素慢性HBV的重要守护者。文章揭示了MAIT细胞依赖MR1的抗HBV潜能，发现结合胆红素是慢性HBV感染患者MAIT细胞频率和功能失调的主要因素，为MAIT细胞免疫抗慢性HBV感染提供了治疗靶点。

在会议中，参会师生就相关内容进行了交流和探讨。此次报告紧紧围绕免疫学技术平台目前开展的科研方向，展示了最新研究前沿和动态；开拓了师生科研思路，为后续课题设计、课题开展提供了指导，同时也锻炼了师生SCI论文的阅读、分析、写作能力，浓厚了免疫学技术平台的学术氛围。

Mucosal-Associated Invariant T Cell Dysregulation Correlates With Conjugated Bilirubin Level in Chronic HBV Infection

BACKGROUND AND AIMS: Mucosal-associated invariant T (MAIT) cells are nonconventional T cells restricted to major histocompatibility complex class I–related protein 1 (MR1). They are highly abundant in human liver and activated by T-cell receptor (TCR)-dependent and TCRindependent mechanisms to exhibit rapid, innate-like effector responses. However, the roles of MAIT cells in chronic HBV infection are still open for study. This study aims to test their antiviral potential and investigate their dynamic changes and regulating factors during chronic HBV infection.

APPROACH AND RESULTS: Blood samples from 257 chronic HBV-infected patients were enrolled, and nontumor liver specimens were collected from 58 HBV-infected HCC patients. Combining cell-culture experiments and human data, we showed that MAIT cells had strong cytotoxicity against HBV-transfected hepatocytes in an MR1-dependent way. However, circulating and hepatic MAIT cells in HBVinfected patients decreased significantly compared to controls. Correlation analysis suggested that MAIT cell frequency was associated with disease progression and inversely correlated with serum-conjugated bilirubin level. In particular, conjugated bilirubin not only directly promoted MAIT cell activation and apoptosis, but also impaired TCR-induced proliferation and expansion of MAIT cells, which could be partially rescued by IL-2 in the absence of conjugated bilirubin. Despite that MAIT cells from patients with high conjugated bilirubin levels showed decreased cytokine-producing capacity, the increased TCR-dependent antiviral cytokine production suggested MAIT cells as an important guardian of chronic HBV with high conjugated bilirubin.

CONCLUSIONS: We reveal the MR1-dependent, anti-HBV potential of MAIT cells and identify conjugated bilirubin as a major factor dysregulating its frequency and function in chronic HBV-infected patients, suggesting a therapeutic target for MAIT-cell–based immunity against chronic HBV infection. (Hepatology 2021;73:1671-1687).

图/文 徐文峰