通过抗原依赖和依赖因子调控Tim-3表达对慢性乙型肝炎病毒感

StephenW

Front Cell Infect Microbiol. 2017 Mar 28;7:98. doi: 10.3389/fcimb.2017.00098. eCollection 2017.
Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection.
Dong J1, Yang XF2, Wang LX2, Wei X2, Wang AH3, Hao CQ2, Shen HJ2, Huang CX2, Zhang Y2, Lian JQ2.
Author information

1    Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China; Department of Ophthalmology and Otorhinolaryngology, Tenth Hospital of PLAWuwei, China.
2    Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
3    Department of Epidemiology, School of Public Health, Fourth Military Medical University Xi'an, China.

Abstract

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.
KEYWORDS:

T cell receptor; T-cell immunoglobulin domain and mucin domain-containing molecule-3; common γ-chain cytokines; hepatitis B virus; immunomodulation

PMID:
    28401068
PMCID:
    PMC5368241
DOI:
    10.3389/fcimb.2017.00098

StephenW

前细胞感染微生物2017年3月28日; 7：98。 doi：10.3389 / fcimb.2017.00098。 eCollection 2017。
通过抗原依赖和依赖因子调控Tim-3表达对慢性乙型肝炎病毒感染患者的T细胞的影响。
Dong J1，Yang XF2，Wang LX2，Wei X2，Wang AH3，Hao CQ2，Shen HJ2，Huang CX2，Zhang Y2，Lian JQ2。
作者信息

1中国第四军医大学唐都医院传染病中心;中国普陀威第十医院眼科与耳鼻咽喉科。
2中国西安第四军医大学唐都医院传染病中心。
3中国西安第四军医大学公共卫生学院流行病学系。

抽象

T细胞免疫球蛋白结构域和含有粘蛋白结构域的分子-3（Tim-3）在病毒特异性T细胞上被上调，并在慢性乙型肝炎病毒（HBV）感染中导致T细胞耗尽。然而，Tim-3表达的调节仍未完全阐明。为了评估Tim-3表达在T细胞上的潜在病毒和炎症因子，76例慢性HBV感染患者（包括40例慢性乙型肝炎[CHB]和36例无症状HBV携带者[AsC]）和40例正常对照（NC）入选本研究。针对HBV编码抗原，HBV肽库和通过流式细胞术刺激的普通γ链（γc）细胞因子，评估CD4 +和CD8 + T细胞上的Tim-3表达。 HBV肽和抗CD3 / CD28直接诱导T细胞上的Tim-3表达。 γc细胞因子也驱动慢性HBV感染患者CD4 +和CD8 + T细胞上Tim-3上调。然而，γc细胞因子没有通过抗CD3 / CD28或HBV肽刺激来增强Tim-3诱导。此外，γc细胞因子介导的Tim-3诱导不能被γc细胞因子受体中和抗体消除。目前的结果表明，慢性乙型肝炎病毒感染患者T细胞上的Tim-3表达升高可以通过抗原依赖和依赖性方式调节。 γc细胞因子在调节抑制途径中的作用可能被评估为人类免疫治疗。
关键词：

T细胞受体; T细胞免疫球蛋白结构域和含粘蛋白结构域的分子-3;常见的γ链细胞因子;乙型肝炎病毒;免疫调节

PMID：
    28401068
PMCID：
    PMC5368241
DOI：
    10.3389 / fcimb.2017.00098