PD-1 upregulation is associated with HBV specific T cell dysfunction in chronic hepatitis B patients

被引:198
作者
Peng, Guoping [1 ]
Li, Shuping [1 ]
Wu, Wei [1 ]
Tan, Xufei [1 ]
Chen, Yiqiong [2 ]
Chen, Zhi [1 ]
机构
[1] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Inst Infect Dis,Key Lab Hlth Minist, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Univ, Coll Med, Inst Immunol, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
chronic hepatitis B; PD-L1; pentamer; serum viral load; blockade;
D O I
10.1016/j.molimm.2007.07.038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Programmed death-1 (PD-1) is demonstrated to have an increased expression on antigen-specific T cells during chronic virus infections, and the blockage of PD-1/PD-ligand (PD-L1) pathway could restore the function of exhausted T cells. We measured the PD-1 expression levels on HBV-specific CD8 T cells and investigated the role of PD-1/PD-L1 pathway in T-cell responses of patients with different HBV infection statuses. Compared to the patients with convalescent acute hepatitis B, PD-1 expression on total CD8 T cells from chronic hepatitis B (CHB) patients was significantly upregulated, especially on the HBV pentamer-positive CD8 T cells. And PD-L1, but not PD-L2, was also significantly upregulated on PBMC from CHB patients. In CHB patients, HBV-specific T cells and cellular proliferation could be observed under the recombinant HBV-Ag stimulation in vitro, and blockade of PD-1 pathway significantly enhanced the IFN-gamma production and cellular proliferation of PBMC. Furthermore, PD-1 expression level on HBV-pentamers positive CD8 T cells was positively associated with plasma viral load in CHB patients. Thus, PD-1 upregulation on HBV-specific CD8 T cells is engaged in the dysfunction of T cells and high viraemia in CHB patients, and the antiviral T-cell responses could be improved by the blockade of this inhibitory PD-1/PD-L1 pathway. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:963 / 970
页数:8
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