肝脏泡型包虫病患者外周血中调节性T细胞及IL-35的表达水平
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摘要
目的探讨肝脏泡型包虫病患者外周血中调节性T细胞(Treg)及相关细胞因子白介素-35(IL-35)的表达及意义。方法采用流式细胞技术、酶联免疫吸附法(ELISA)对2017年1月至2017年9月四川省人民医院的17例肝脏泡型包虫病患者和17例健康志愿者外周血中Treg细胞和IL-35表达进行检测。结果肝脏泡型包虫病患者外周血中Treg细胞占CD4+~T细胞的比例(CD4~+CD25~+CD127~(low)/CD4~+T cells)为4.68%~10.30%(7.97%±1.47%),对照组为5.09%~9.25%(6.65%±0.99%),2组差异有统计学意义(P<0.05)。肝脏泡型包虫病患者外周血IL-35水平为66.24~101.23 pg/ml(81.26 pg/ml±10.42 pg/ml),对照组IL-35为19.59~79.64 pg/ml(42.61 pg/ml±17.80 pg/ml),差异有统计学意义(P<0.05)。肝脏泡型包虫病患者外周血IL-35与Treg细胞同步升高,并且呈正相关(R=0.566 7,P=0.010 1)。结论肝脏泡型包虫病患者外周血中Treg细胞和IL-35表达水平上调,两者可能与泡型包虫病的发生发展有关。
This study was performed to investigate the expression and role of regulatory T cells(Treg) and interleukin-35(IL-35) in peripheral blood of patients with hepatic alveolar echinococcosis. Total of 17 patients with hepatic alveolar echinococcosis from Sichuan Provincial People's Hospital and 17 healthy volunteers were enrolled in this study from January 2017 to September 2017. Flow cytometry and enzyme-linked immunosorbent assay(ELISA) were employed respectively to detect Treg cells and IL-35 levels in peripheral blood. Data showed that the proportion of Treg cells in CD4~+T cells of peripheral blood of patients with hepatic alveolar echinococcosis was4.68% to 10.30%(7.97% ± 1.47%), and the control group was 5.09% to 9.25%(6.65% ± 0.99%), the difference between the two groups was statistically significant(P<0.05). The level of IL-35 in peripheral blood of patients with hepatic alveolar echinococcosis was 66.24 to101.23 pg/ml(81.26 pg/ml ± 10.42 pg/ml), and the control group was 19.59 to 79.64 pg/ml(42.61 pg/ml±17.80 pg/ml), the difference was statistically significant(P<0.05). In peripheral blood of patients with hepatic alveolar echinococcosis, IL-35 was positively correlated with Treg cells(R=0.5667, P=0.010 1). In conclusion, the expression of Treg and IL-35 in peripheral blood of patients with hepatic alveolar echinococcosis is up-regulated,which may related to the occurrence and development of hepatic alveolar echinococcosis.
This study was performed to investigate the expression and role of regulatory T cells(Treg) and interleukin-35(IL-35) in peripheral blood of patients with hepatic alveolar echinococcosis. Total of 17 patients with hepatic alveolar echinococcosis from Sichuan Provincial People's Hospital and 17 healthy volunteers were enrolled in this study from January 2017 to September 2017. Flow cytometry and enzyme-linked immunosorbent assay(ELISA) were employed respectively to detect Treg cells and IL-35 levels in peripheral blood. Data showed that the proportion of Treg cells in CD4~+T cells of peripheral blood of patients with hepatic alveolar echinococcosis was4.68% to 10.30%(7.97% ± 1.47%), and the control group was 5.09% to 9.25%(6.65% ± 0.99%), the difference between the two groups was statistically significant(P<0.05). The level of IL-35 in peripheral blood of patients with hepatic alveolar echinococcosis was 66.24 to101.23 pg/ml(81.26 pg/ml ± 10.42 pg/ml), and the control group was 19.59 to 79.64 pg/ml(42.61 pg/ml±17.80 pg/ml), the difference was statistically significant(P<0.05). In peripheral blood of patients with hepatic alveolar echinococcosis, IL-35 was positively correlated with Treg cells(R=0.5667, P=0.010 1). In conclusion, the expression of Treg and IL-35 in peripheral blood of patients with hepatic alveolar echinococcosis is up-regulated,which may related to the occurrence and development of hepatic alveolar echinococcosis.
引文
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[18]Liu F,Tong F,He Y,et al.Detectable expression of IL-35in CD4+T cells from peripheral blood of chronic hepatitis B patients[J].Clin Immunol,2011,139(1):1-5.
[19]Kochetkova I,Golden S,Holderness K,et al.IL-35Stimulation of CD39+regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10[J].J Immunol,2010,184(12):7144-7153.
[20]Liu JQ,Liu Z,Zhang X,et al.Increased Th17 and regulatory T cell responses in EBV-induced gene3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis[J].J Immunol,2012,188(7):3099-31006.
[21]Olson BM,Jankowskagan E,Becker JT,et al.Human prostate tumor antigen-specific CD8+regulatory T cells are inhibited by CTLA-4 or IL-35 blockade[J].J Immunol,2012,189(12):5590-5601.
[22]Vuitton DA,Gottstein B.Echinococcus multilocularis and its intermediate host:a model of parasite-host interplay[J].J Biomed Biotechnol,2010,2010(1):923193.
[2]Kawamura N,Kamiyama T,Sato N,et al.Long-term results of hepatectomy for patients with alveolar echinococcosis:a single-center experience[J].J Am Coll Surg,2011,212(5):804-812.
[3]Rigano R,Buttari B,de Falco E,et al.Echinococcus granulosus-specific T-cell lines derived from patients at various clinical stages of cystic echinococcosis[J].Parasite Immunol,2004,26(1):45-52.
[4]Tuxun T,Wang JH,Lin RY,et al.Th17/Treg imbalance in patients with liver cystic echinococcosis[J].Parasite Immunol,2012,34(11):520-527.
[5]Sakaguchi S,Yamaguchi T,Nomura T,et al.Regulatory T cells and immune tolerance[J].Cell,2008,133(5):775-787.
[6]史国星,曾强,窦剑,等.CD4+C25+Foxp3+调节性T细胞在自身免疫性疾病中的研究进展[J].免疫学杂志,2016,32(12):1092-1095.
[7]吴梦,陈献,娄鉴芳,等.TGF-β1调控卵巢癌微环境中CD8+Treg的表型及功能初探[J].免疫学杂志,2016,32(12):1058-1062.
[8]Collison LW,Workman CJ,Kuo TT,et al.The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J].Nature,2007,450(7169):566-569.
[9]Siracusano A,Delunardo F,Teggi A,et al.Cystic echinococcosis:aspects of immune response,immunopathogenesis and immune evasion from the human host[J].Endocrine,2012,12(12):16-23.
[10]Facciabene A,Motz GT,Coukos G.T-regulatory cells:key players in tumor immune escape and angiogenesis[J].Cancer Res,2012,72(9):2162-2171.
[11]Belkaid Y,Sun CM,Bouladoux N.Parasites and immunoregulatory T cells[J].Curr Opin Immunol,2006,18(4):406-412.
[12]Bardel E,Larousserie F,Charlot Rabiega P,et al.Human CD4+CD25+Foxp3+regulatory T cells do not constitutively express IL-35[J].J Immunol,2008,181(10):6898-6905.
[13]Li X,Mai J,Virtue A,et al.IL-35 is a novel responsive anti-inflammatory cytokine-a new system of categorizing anti-inflammatory cytokines[J].PLo S One,2012,7(3):e33628.
[14]Sawant DV,Hamilton K,Vignali DA.Interleukin-35:expanding its job profile[J].J Interferon Cytokine Res,2015,35(7):499-512.
[15]Collison LW,Chaturvedi V,Henderson AL,et al.IL-35-mediated induction of a potent regulatory T cell population[J].Nat Immunol,2010,11(12):10931101.
[16]Castellani ML,Anogeianaki A,Felaco P,et al.IL-35,an anti-inflammatory cytokine which expands CD4+CD25+Treg cells[J].J Biol Regul Homeost Agents,2010,24(2):131-135.
[17]Collison LW,Pillai MR,Chaturvedi V,et al.Regulatory T cell suppression is potentiated by target T cells in a cell contact,IL-35-and IL-10-dependent manner[J].J Immunol,2009,182(10):6121-6128.
[18]Liu F,Tong F,He Y,et al.Detectable expression of IL-35in CD4+T cells from peripheral blood of chronic hepatitis B patients[J].Clin Immunol,2011,139(1):1-5.
[19]Kochetkova I,Golden S,Holderness K,et al.IL-35Stimulation of CD39+regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10[J].J Immunol,2010,184(12):7144-7153.
[20]Liu JQ,Liu Z,Zhang X,et al.Increased Th17 and regulatory T cell responses in EBV-induced gene3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis[J].J Immunol,2012,188(7):3099-31006.
[21]Olson BM,Jankowskagan E,Becker JT,et al.Human prostate tumor antigen-specific CD8+regulatory T cells are inhibited by CTLA-4 or IL-35 blockade[J].J Immunol,2012,189(12):5590-5601.
[22]Vuitton DA,Gottstein B.Echinococcus multilocularis and its intermediate host:a model of parasite-host interplay[J].J Biomed Biotechnol,2010,2010(1):923193.