31例多发性硬化患者T淋巴细胞亚群及相关细胞因子的检测
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摘要
目的:探讨多发性硬化(MS)患者静脉血T淋巴细胞亚群及相关细胞因子的意义。方法:采用流式细胞术(FCM)检测31例MS患者治疗前(MS组)、泼尼松治疗4周后(泼尼松组)及20例健康者(正常组)外周血Th1(CD4~+IFN-γ~+)、Th2(CD4~+IL-4~+)、Th17(CD4~+IL-17~+)、Treg(CD4~+FoxP3~+)、Tc1(CD4-CD8~+IFN-γ~+)和Tc2(CD4-CD8~+IL-4~+)T淋巴细胞亚群变化;流式微球芯片捕获技术(CBA)检测血浆细胞因子IFN-γ、TNF-α、IL-17A、IL-4和IL-10的含量。结果:(1)FCM分析结果显示,与正常组比较,MS组Th1细胞和Th17细胞均明显升高(P<0.05);Treg细胞和Tc1细胞显著下降(P<0.01),Th17/Treg比例明显升高(P<0.01);与MS组比较,泼尼松组Tc1、Tc2和Treg细胞百分率均明显升高(P<0.01),而Th1和Th17细胞显著下降(P<0.05),Th17/Treg比值降低(P<0.01);(2)CBA法检测结果显示,与正常组比较,MS组IFN-γ和IL-17A含量升高(P<0.05;P<0.01),IL-4和IL-10含量明显降低(P<0.01);与MS组比较,泼尼松组IL-17A含量明显降低(P<0.01),IL-4和IL-10均显著升高(P<0.01)。结论:MS的发生可能主要与Th17上调和Treg下调有关,提示临床上针对MS靶向下调Th17和上调Treg,纠正Th17/Treg比例失衡,具有潜在应用价值。
Objective: To investigate the levels of T lymphocyte subsets and related cytokines in 31 cases of the patients with multiple sclerosis(MS)and their significance to clinic. Methods: The lymphocyte subsets including Th1(CD4~+IFN-γ~+),Th17(CD4~+IL-17~+),Treg(CD4~+FoxP3~+),Tc1(CD4-CD8~+IFN-γ~+)and Tc2(CD4-CD8~+IL-4~+)in peripheral blood mononuclear cells were determined by flow cytometry in three different groups;concentrations of plasma cytokines including IFN-γ,TNF-α,、IL-17 A,IL-4 and IL-10 were determined by cytometric bead array. Results: Compared with normal control group,the percentages of Th1 and Th17 cells wereincreased significantly(P<0.05),while Treg and Tc1 cells were decreased significantly(P<0.01),the proportion of Th17/Treg was increased significantly in MS group(P<0.01);compared with MS group, the percentages of Tc1,Tc2 andTreg cells were increased significantly(P<0.05),while Th17 and Th1 cells were reduced significantly(P<0.01),and the proportion of Th17/Treg was reduced significantly(P<0.01)in Prednisone group;Compared with normal control group,the concentration of IFN-γ and IL-17 A were increased significantly(P<0.05;P<0.01), while the concentration of IL-4 and IL-10 were decreased significantly in MS group(P<0.01); compared with MS group, the concentration of IL-17 A were decreased obviously(P<0.05;P<0.01), while the concentration of IL-4 and IL-10 were increased significantly in prednisone group(P <0.01).Conclusion: The mechanism of multiple sclerosis might relate to Treg down-regulation,and Th17 cells up-regulation.Experiments in this paper show that it has potential application value forTreg up-regulation,and Th17 cells down-regulation,which could be used asan immunomdulatory therapy in the patients with clinical multiple sclerosis.
Objective: To investigate the levels of T lymphocyte subsets and related cytokines in 31 cases of the patients with multiple sclerosis(MS)and their significance to clinic. Methods: The lymphocyte subsets including Th1(CD4~+IFN-γ~+),Th17(CD4~+IL-17~+),Treg(CD4~+FoxP3~+),Tc1(CD4-CD8~+IFN-γ~+)and Tc2(CD4-CD8~+IL-4~+)in peripheral blood mononuclear cells were determined by flow cytometry in three different groups;concentrations of plasma cytokines including IFN-γ,TNF-α,、IL-17 A,IL-4 and IL-10 were determined by cytometric bead array. Results: Compared with normal control group,the percentages of Th1 and Th17 cells wereincreased significantly(P<0.05),while Treg and Tc1 cells were decreased significantly(P<0.01),the proportion of Th17/Treg was increased significantly in MS group(P<0.01);compared with MS group, the percentages of Tc1,Tc2 andTreg cells were increased significantly(P<0.05),while Th17 and Th1 cells were reduced significantly(P<0.01),and the proportion of Th17/Treg was reduced significantly(P<0.01)in Prednisone group;Compared with normal control group,the concentration of IFN-γ and IL-17 A were increased significantly(P<0.05;P<0.01), while the concentration of IL-4 and IL-10 were decreased significantly in MS group(P<0.01); compared with MS group, the concentration of IL-17 A were decreased obviously(P<0.05;P<0.01), while the concentration of IL-4 and IL-10 were increased significantly in prednisone group(P <0.01).Conclusion: The mechanism of multiple sclerosis might relate to Treg down-regulation,and Th17 cells up-regulation.Experiments in this paper show that it has potential application value forTreg up-regulation,and Th17 cells down-regulation,which could be used asan immunomdulatory therapy in the patients with clinical multiple sclerosis.
引文
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[4] Ishizu T, Osoegawa M, Mei F J, et al. Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis[J].Brain,2005, 128(5):988
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[8]陈祚珈,高雅懿,李志远,等. FOXP3+调节性T细胞[J].生命科学,2010,22(6):515
[9] Ghannam S, Pene J, Torcy-Moquet G, et al. Mesenchymal stem cells inhibit human th17cell differentiation and function and induce a T regulatory cell phenotype[J].J Immunol, 2010, 185(1):302
[10] Wang J H, Wang G Y, Sun B, et al. Interleukin-27 suppresses experimental autoimmune encephalomyelitis during bone marrow stromal cell treatment[J].J Autoimmunity, 2008, 30(4):222
[11] Bai L, Lennon D P, Eaton V, et al. Human bone marrow-derived mesenchymal stem cells induce th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis[J].Glia, 2009, 57(11):1192
[12] Darlington P J, Boivin M N, Renoux C, et al. Reciprocal th1 and th17 regulation by mesenchymal stem cells:implication for multiple sclerosis[J]. Annals of Neurology, 2010,68(4):540
[13] Kang J W, Koo H C, Hwang S Y, et al. Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells[J].J Vet Sci, 2012, 13(1):23
[2]李晓玲,张博,于春梅,等. Th17/Treg细胞在复发缓解型多发性硬化中的表达[J].中国神经免疫学和神经病学杂志, 2015, 22(3):153
[3] Tsang J, Lu L, Jiang S P. TH17 cells in organ transplantation rejection and tolerance[J]. TH17 Cells in Health and Disease, 2011, 319
[4] Ishizu T, Osoegawa M, Mei F J, et al. Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis[J].Brain,2005, 128(5):988
[5]李丹,方宁,陈代雄,等.人羊膜上皮细胞治疗大鼠实验性自身免疫性脑脊髓炎的效应及免疫调节作用[J].中国免疫学杂志,2013, 29(10):1011
[6]方宁,李丹,余丽梅,等.人羊膜间充质干细胞对大鼠实验性自身免疫性脑脊髓炎的疗效及免疫调节作用[J].免疫学杂志, 2014,30(1):6
[7] Mills K H. Designer adjuvants for enhancing the efficacy of infectious disease and cancer vaccines based on suppression of regulatory T cell induction[J].Immunol Lett, 2009,122(2):108
[8]陈祚珈,高雅懿,李志远,等. FOXP3+调节性T细胞[J].生命科学,2010,22(6):515
[9] Ghannam S, Pene J, Torcy-Moquet G, et al. Mesenchymal stem cells inhibit human th17cell differentiation and function and induce a T regulatory cell phenotype[J].J Immunol, 2010, 185(1):302
[10] Wang J H, Wang G Y, Sun B, et al. Interleukin-27 suppresses experimental autoimmune encephalomyelitis during bone marrow stromal cell treatment[J].J Autoimmunity, 2008, 30(4):222
[11] Bai L, Lennon D P, Eaton V, et al. Human bone marrow-derived mesenchymal stem cells induce th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis[J].Glia, 2009, 57(11):1192
[12] Darlington P J, Boivin M N, Renoux C, et al. Reciprocal th1 and th17 regulation by mesenchymal stem cells:implication for multiple sclerosis[J]. Annals of Neurology, 2010,68(4):540
[13] Kang J W, Koo H C, Hwang S Y, et al. Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells[J].J Vet Sci, 2012, 13(1):23