滤泡性辅助性T细胞与HCV感染的相关性

王宇; 马志远; 郭永红; 何瑜; 张颖; 谢玉梅; 马力; 周云; 贾战生

滤泡性辅助性T细胞与HCV感染的相关性

第四军医大学唐都医院全军感染病诊疗中心

基金项目:

国家自然科学基金项目(81170389)；

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中图分类号: R512.63
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出版历程
- 出版日期: 2013-05-20

Investigation of CD4+CXCR5+ follicular helper T cell frequency and expression of related functional molecules in peripheral blood of hepatitis C virus patients

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摘要

摘要:
目的检测慢性HCV感染者外周血CD4+T细胞中滤泡性辅助性T细胞（Tfh）所占比例,ICOS及负性调控因子PD-1、Tim-3在Tfh细胞上的表达。方法以31例HCV感染者、9例HCV感染自愈者（SR-HCV患者）及12例健康志愿者作为研究对象,应用流式细胞术分析外周血中CD4+CXCR5+Tfh细胞在CD4+T细胞中所占比率,同时检测其ICOS、PD-1及Tim-3分子表达,通过酶联免疫吸附法测定血浆中白细胞介素（IL）21及HCV抗体水平,实时定量PCR检测HCV RNA滴度;多组数据比较采用单因素方差分析,双变量之间相关性采用Spearman秩相关分析。结果与健康对照组相比,HCV感染者及自愈者外周血CD4+T细胞比率升高（P<0.05）;HCV感染者CD4+CXCR5+Tfh细胞比率高于自愈及健康对照（P<0.05）;HCV感染及自愈者CD4+CX-CR5+Tfh细胞ICOS、PD-1、Tim-3显著高于健康对照（P<0.05）;血清il-21水平hcv感染者与健康对照无统计学差异（p>0.05）;HCV感染者HCV RNA载量与Tfh细胞比例呈负相关。...
- T淋巴细胞,辅助诱导 /
- 肝炎,丙型
Abstract:
Objective To determine whether hepatitis C virus (HCV) infection is associated with increased frequency of the CD4+ follicular helper T (Tfh) subset in peripheral blood and to investigate their potential function contribution to the HCV-induced immune response by measuring expression levels of the Tfh cell-related molecules inducible T cell costimulator (ICOS) , programmed death-1 (PD-1) , and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) .Methods Thirty-one patients with chronic HCV and nine patients with spontaneously resolved (SR) -HCV infection, all without prior (six months) treatment, were recruited for study.Twelve healthy individuals were recruited for use as controls.Peripheral blood samples of cases and controls were collected.Peripheral blood mononuclear cells were isolated and subjected to flow cytometry to measure the frequency of Tfh cells (by detecting CD4+CXCR5+) and their surface expression of ICOS, PD-1, and Tim-3.Serum concentrations of IL-21 and HCV antibodies were detected by enzyme-linked immunosorbent assay and of globin by an automated biochemistry analyzer.The HCV RNA titer was quantified by real-time PCR.Multiple comparisons were made by one-way ANOVA test, and correlation analysis was carried out by Spearman′s rank correlation test.Results All HCV-infected patients, including the SR-HCV cases, showed a significantly higher CD4+ T cell ratio, than the healthy controls (both P<0.05) ;however, the chronic HCV patients showed a significantly higher CD4+CXCR5+ ratio than the SR-HCV cases and healthy controls (both P<0.05) .All HCV-infected patients, including the SR-HCV cases, showed significantly higher levels of ICOS+/PD-1+/Tim-3+ cells in the CD4+CXCR5+ Tfh cells than the healthy controls (all P<0.05) .the="" hcv-infected="" patients="" showed="" but="" not="" lower="" levels="" of="" serum="" il-21="" than="" the="" healthy="" controls="" both="" p="">0.05) .The HCV RNA load was inversely correlated to frequency of CD4+CXCR5+ Tfh cells.Conclusion HCV infection is associated with increased frequency of Tfh cells, which may contribute functionally to the anti-viral immune response in a manner distinctive from the CD4+ (IL-21-producing) parent population.
- T-lymphocytes /
- helper-inducer

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参考文献(14)

[1]Rehermann B.Chronic infections with hepatotropic viruses:mecha-nisms of impairment of cellular immune responses[J].Semin LiverDis, 2007, 27 (2) :152-160.

[2] Huang XJ, Lv X.Progress in hepatitis C vaceine[J].Int J Virol, 2011, 18 (1) :29-32. (in Chinese) 黄小军, 吕欣.丙型肝炎疫苗研究进展[J].国际病毒学杂志, 2011, 18 (1) :29-32.

[3] Feng J, Hu X, Guo H, et al.Patients with chronic hepatitis C expressa high percentage of CD4 (+) CXCR5 (+) T follicular helper cells[J].J Gastroenterol, 2012, 47 (9) :1048-1056.

[4]Rodríguez Pinilla SM, Roncador G, Rodríguez-Peralto JL, et al.Pri-mary cutaneous CD4+small/medium-sized pleomorphic t-cell lym-phoma expresses follicular T-cell markers[J].Am J Surg Pathol, 2009, 33 (1) :81-90.

[5]Simpson N, Gatenby PA, Wilson A, et al.Expansion of circulating Tcells resembling follicular helper T cells is a fixed phenotype that iden-tifies a subset of severe systemic lupus erythematosus[J].ArthritisRheum, 2010, 62 (1) :234-244.

[6]Rodríguez-Pinilla SM, Atienza L, Murillo C, et al.Peripheral T-cell lymphoma with follicular T-cell markers[J].Am J SurgPathol, 2008, 32 (12) :1787-1799.

[7]Feng JY, Lu L, Hua C, et al.High frequency of CD4+CXCR5+TFHcells in patients with immuneactive chronic hepatitis B[J].PLoS ONE, 2011, 6 (7) :e21698.

[8]Moreno C, Deltenre P.Management of chronic hepatitis C in 2012 inBelgium[J].Rev Med Brux, 2012, 33 (4) :223-227.

[9]Kim CH, Rott LS, Clark-Lewis I, et al.Subspecialization of CX-CR5+T Cells:B helper activity isfocused in a germinal center–localized subset of CXCR5+T Cells[J].J Exp Med, 2001, 193 (12) :1373-1381.

[10]Feng JY, Lu L, Hua C, et al.High frequency of CD4+CXCR5+TFHcells in patients with immuneactive chronic hepatitis B[J].PLoS ONE, 2011, 6 (7) :e21698.

[11]Linterman MA, Vinuesa CG.T Follicular Helper Cells During Im-munity and Tolerance[J].Prog Mol Biol Transl Sci, 2010, 92:207-248.

[12]Chen M, Guo Z, Ju W, et al.The development and function offollicular helper T cells in immune responses[J].Cell Mol Immu-nol, 2012, 9 (5) :375-379.

[13]Deenick EK, Ma CS.The regulation and role of T follicular helpercells in immunity[J].Immunology, 2011, 134 (4) :361-367.

[14]Wang Y, Zhang Y, Jia ZS.Recent treatment advances for hepatitisC virus-related mixed cryoglobulinemia[J].J Clini Hepatol, 2012, 28 (8) :628-632 (in Chinese) 王宇, 张颖, 贾战生.丙型肝炎病毒相关性混合型冷球蛋白血症的治疗进展[J].临床肝胆病杂志, 2012, 28 (8) :628-632.

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