Immune Checkpoint Molecules Expressed on CD4(+) T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative.
Immune Checkpoint Molecules Expressed on CD4(+) T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative.
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乙型肝炎 e 抗原阴性的慢性无症状乙型肝炎病毒携带者 CD4 T 细胞亚群表达的免疫检查点分子
DOI：
10.3389/fmicb.2022.887408
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性B型肝炎病毒（HBV）感染仍然是世界范围内的主要公共卫生问题。CD 4 + T细胞上表达的免疫检查点分子在慢性HBV感染中起关键作用。然而，它们在慢性无症状HBV携带者（ASCs）与肝炎B e抗原（HBeAg）阴性的作用仍然不清楚。在这项研究中，我们探讨了在HBeAg阴性的慢性ASC中CD 4 + T细胞亚群上表达的免疫检查点分子的作用。分离HBeAg阴性ASCs和健康对照（HC）的人外周血单个核细胞（PBMC），采用流式细胞术检测CD 4 + T细胞亚群上免疫检查点分子的表达和血清细胞因子的表达。此外，通过实时定量PCR测定分析免疫检查点分子的mRNA表达。与HC相比，CD 4 + T细胞在HBeAg阴性的慢性ASC的PBMC中高度表达LAG-3、TIM-3和PD-1。有趣的是，在ASCs中，TIM-3和PD-1在循环滤泡辅助性T（Tfh）细胞上的表达显著高。此外，LAG-3、TIM-3和PD-1的高表达在Treg、Th 1、Th 2和Th 17细胞中是不同的。另外，ASCs PBMC中TIM-3和CTLA-4 mRNA表达明显升高。然而，来自ASC的PBMC中CTLA-4+ CD 4 + T细胞亚群的频率与HC没有差异。ASCs血清中6种细胞因子水平与HC无明显差异。CD 4 + T细胞亚群上高表达的免疫检查点分子在HBeAg阴性的慢性ASCs中起重要作用，为慢性HBV感染的发病机制提供了潜在的治疗靶点。
Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4+ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4+ T cell subsets in chronic ASCs with HBeAg-negative. Human peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4+ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay. In comparison with HC, CD4+ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4+CD4+ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC. Immune checkpoint molecules highly expressed on CD4+ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.
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慢性乙型肝炎病毒感染患者 T 细胞上抗原依赖性和非依赖性因子对 Tim-3 表达的调节
影响因子：
5.7
作者：
Dong J;Yang XF;Wang LX;Wei X;Wang AH;Hao CQ;Shen HJ;Huang CX;Zhang Y;Lian JQ
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Lian JQ
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Jiang, Yanfang
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Bengsch, Bertram;Martin, Bianca;Thimme, Robert
通讯作者：
Thimme, Robert
影响因子：
3.9
作者：
Jin X;Yan ZH;Lu L;Lu S;Zhang G;Lin W
通讯作者：
Lin W
影响因子：
29.4
作者：
Park JJ;Wong DK;Wahed AS;Lee WM;Feld JJ;Terrault N;Khalili M;Sterling RK;Kowdley KV;Bzowej N;Lau DT;Kim WR;Smith C;Carithers RL;Torrey KW;Keith JW;Levine DL;Traum D;Ho S;Valiga ME;Johnson GS;Doo E;Lok AS;Chang KM;Hepatitis B Research Network
通讯作者：
Hepatitis B Research Network