CD8+T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides

被引:24
作者
Barathan, Muttiah [1 ]
Mohamed, Rosmawati [2 ]
Vadivelu, Jamuna [1 ]
Chang, Li Yen [1 ]
Vignesh, Ramachandran [3 ]
Krishnan, Jayalakshmi [4 ]
Sigamani, Panneer [5 ]
Saeidi, Alireza [1 ]
Ram, M. Ravishankar [1 ]
Velu, Vijayakumar [6 ]
Larsson, Marie [7 ]
Shankar, Esaki M. [1 ,4 ,8 ]
机构
[1] Univ Malaya, Fac Med, Dept Med Microbiol, Kuala Lumpur 50603, Malaysia
[2] Univ Malaya, Dept Med, Kuala Lumpur 50603, Malaysia
[3] Univ Kuala Lumpur, Royal Coll Med Perak UniLK CRCMP, Lab Based Dept, Ipoh, Malaysia
[4] CUTN, Sch Basic & Appl Sci, Dept Life Sci, Div Infect Biol, Thiruvarur 610005, India
[5] CUTN, Dept Social Work, Thiruvarur 610005, India
[6] Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30329 USA
[7] Linkoping Univ, Dept Clin & Expt Med, Div Mol Virol, S-58185 Linkoping, Sweden
[8] Univ Malaya, Ctr Excellence Res AIDS CERiA, Kuala Lumpur 50603, Malaysia
基金
瑞典研究理事会;
关键词
Co-inhibitory receptors; HCV; Immune checkpoint; PD-1; TIM-3; T-cell exhaustion; INVARIANT T-CELLS; C VIRUS-INFECTION; VIRAL PERSISTENCE; EXHAUSTION; BLOCKADE; TIM-3; PD-1; CD4(+); CLEARANCE; CYTOKINES;
D O I
10.1016/j.cellimm.2016.12.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray (TM) following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-beta 1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-alpha, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:1 / 9
页数:9
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