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Decreased Vδ2 γδ T cells associate with liver damage through regulating Th17 response in chronic hepatitis B patients
Xiaoli Wu1,**,
Ji-Yuan Zhang2,**,
Ang Huang2,
Yuan-Yuan Li2,
Song Zhang1,
Jun Wei1,
Siyuan Xia1,
Yajuan Wan1,
Weiwei Chen2,
Zheng Zhang2,
Yangguang Li1,
Ti Wen1,
Yan Chen2,
Yoshimasa Tanaka3,
Youjia Cao1,
Puyue Wang1,
Liqing Zhao1,
Zhenzhou Wu1,
Zheng Zhang2,
Fu-Sheng Wang2,* and
Zhinan Yin1,*
- Author Affiliations
1State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China
2Research Center for Biological Therapy, Institute of Translational Hepatology, Beijing 302 Hospital, 100039, China
3Center for Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University1-14 Bunkyo-Cho, Nagasaki, 852-8521, Japan
Corresponding author: Correspondence and reprint requests to Prof. Zhinan Yin, Ph.D., M.D., College of Life Sciences, Nankai University, Tianjin 300071, China. Telephone and Fax: 86-22-23503270, E-mail address: [email protected]; Prof. Fu-Sheng Wang, Ph.D., M.D., Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China. Tel: 86-010-63879735, Fax: 86-010-63879735, Email: [email protected]
↵* These authors are co-responding authors.
↵** These authors contributed equally to this work.
Abstract
Background. γδ T cells comprise a small subset of T cells and play a protective role against cancer and viral infections; however, their precise role in patients with chronic hepatitis B (CHB) remains unclear.
Methods. Flow cytometry and immunofunctional assays were performed to analyze the impact of Vδ2 γδ T cells in 64 immune-activated (IA) patients, 22 immune-tolerant (IT) carriers and 30 healthy controls (HCs).
Results. The frequencies of peripheral and hepatic Vδ2 γδ T cells decreased with disease progression from IT to IA. In IA patients, the decreases in peripheral and intrahepatic frequencies of Vδ2 γδ T cells reversely correlated with ALT levels and histological activity index. These activated terminally differentiated meomory phenotypic Vδ2 γδ T cells exhibited impaired abilities in proliferation and chemotaxis, while maintained a relative intact IFN-γ production. Importantly, Vδ2 γδ T cells, in vitro, significantly suppressed the production of IL-17-producing CD4+ T (Th17) cells associated cytokines in both cell contact-dependent and IFN-γ-dependent mechanisms.
Conclusion. Inflammatory microenvironment in IA patients result in the decreased numbers of Vδ2 γδ T cells, which provide a novel role of Vδ2 γδ T cells through regulating pathogenic Th17 response to protect liver in CHB patients.
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发表于 2013-7-17 21:05
