Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection.
Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus 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
DOI：
10.3389/fcimb.2017.00098
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发表时间：
2017
影响因子：
5.7
通讯作者：
Lian JQ
中科院分区：
文献类型：
--
作者：
Dong J;Yang XF;Wang LX;Wei X;Wang AH;Hao CQ;Shen HJ;Huang CX;Zhang Y;Lian JQ
T细胞免疫球蛋白结构域和粘蛋白结构域包含分子-3(Tim-3)在病毒特异性T细胞上表达上调，在慢性乙肝病毒感染过程中导致T细胞耗竭。然而，TIM-3表达的调控机制仍未完全阐明。为探讨病毒和炎症因素在T细胞TIM-3表达诱导中的作用，选择76例慢性乙肝患者(其中慢性乙型肝炎40例，无症状携带者36例)和40例正常对照(NCS)作为研究对象。用流式细胞仪检测TIM-3在乙肝病毒编码抗原、乙肝病毒多肽库和共同γ链(γc)细胞因子刺激下的表达。乙肝病毒多肽和抗CD3/CD28抗体直接诱导T细胞TIM-3表达。在慢性γ感染患者中，HBVc细胞因子也促使TIM-3上调CD4T细胞和CD8T细胞。然而，γc细胞因子不能增强抗CD3CD2 8或HBV多肽刺激的TIM 3的诱导作用。此外，γc细胞因子受体中和抗体不能阻断γc细胞因子介导的TIM-3诱导。结果提示，慢性乙肝患者T细胞表面TIM-3表达的升高可能受抗原依赖和非抗原依赖两种方式的调节。γ-c细胞因子在抑制途径调节中的作用可作为免疫治疗的评价指标。
T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3 expression was still not fully elucidated. To evaluate the potential viral and inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76 patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and 36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled in this study. Tim-3 expressions on CD4+ and CD8+ T cells were assessed in response to HBV-encoding antigens, HBV peptide pools, and common γ-chain (γc) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28 directly induced Tim-3 expression on T cells. γc cytokines also drive Tim-3 up-regulations on both CD4+ and CD8+ T cells in patients with chronic HBV infection. However, γc cytokines did not enhance the Tim-3 inductions by either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, γc cytokines-mediated Tim-3 induction could not be abrogated by γc cytokine receptor-neutralizing antibodies. The current results suggested that elevation of Tim-3 expression on T cells could be regulated by both antigen-dependent and -independent manner in patients with chronic HBV infection. The role of γc cytokines in modulation of inhibitory pathway might be evaluated as immunotherapies in humans.