Mechanism of gamma-chain cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 in CD8+ T cells of chronic hepatitis B patients
DOI:10.3969/j.issn.1001-5256.2021.05.017
- VernacularTitle:γ链细胞因子对慢性乙型肝炎患者T淋巴细胞免疫球蛋白黏蛋白分子3表达调控的诱导机制
- Author:
Xiaofei YANG
1
;
Linxu WANG
;
Changxing HUANG
;
Jie DONG
;
Haifeng HU
;
Zhanhu BI
;
Jianqi LIAN
;
Ye ZHANG
Author Information
1. Department of Infectious Diseases, The Second Affiliated Hospital of Air Force Medcial University（Tangdu Hospital, Fourth Military Medical University）, Xi’an 710038, China
- Publication Type:Research Article
- Keywords:
Hepatitis B, Chronic;
Cytokines;
CD8-Positive T-Lymphocytes;
T-cell immunoglobulin and mucin domain-containing molecule
- From:
Journal of Clinical Hepatology
2021;37(5):1059-1064.
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism of gamma-chain (γC) cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) in CD8+ T cells of chronic hepatitis B (CHB) patients. MethodsA total of 23 CHB patients who attended Tangdu Hospital, Fourth Military Medical University, from January to May, 2017, were enrolled. Peripheral blood was collected from all patients, and Ficoll density gradient centrifugation was used to isolate peripheral blood mononuclear cells (PBMCs). PBMCs were stimulated with interleukin-7 (IL-7), interleukin-15 (IL-15), and interleukin-21, respectively, and then anti-γC antibody and/or anti-IL-7Rα, anti-IL-2Rβ, and anti-IL-21R were added to the culture solution. After 96 hours of culture, flow cytometry was used to measure the expression of TIM-3, interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon-γ (IFNγ) and the phosphorylation level of signal transducer and activator of transcription (STAT) in CD8+ T cells. A one-way analysis of variance and the least significant difference t-test were used for comparison of continuous data. ResultsThe CD8+ T cells stimulated by IL-7 and IL-15 had a significantly higher percentage of TIM-3-positive CD8+ T cells than those without stimulation (t=9.966 and 9074, P＜0.05), as well as significantly higher expression levels of IL-2, IL-10, and IFN-γ and phosphorylation levels of STAT-5 and STAT-1 (all P＜0.05). Stimulation with anti-IL-7Rα and anti-γC antibody significantly reduced the elevated expression levels of TIM-3, IL-2, and IL-10 in the IL-7 stimulation group (t=5.537, 6.224, and 4.500, P＜0.05). Stimulation with anti-IL-2Rβ alone or in combination with anti-γC antibody significantly reduced the expression levels of TIM-3 and IL-2 and the phosphorylation level of STAT-1 in the IL-15 stimulation group (P ＜0.05). ConclusionIL-7 and IL-15 can upregulate the expression of TIM-3 in CD8+ T cells of CHB patients, possibly via the γC receptor-mediated STAT-cytokine signaling pathway.
