抗原特异性调节性T细胞的诱导及其对动脉粥样硬化的影响

Induction of antigen-specific regulatory T cell and its effect on the formation of atherosclerotic plaque

目的探讨热休克蛋白(HSP)60抗原特异性CD4+CD25+T细胞的体外诱导及其对动脉粥样硬化斑块形成的影响。方法分离apoE-1-小鼠骨髓单个核细胞,经阿司匹林处理培养出未成熟树突状细胞;体外诱导HSP60特异性调节性T细胞分化,检测其百分比和分泌功能;通过混合淋巴细胞反应研究CD4+CD25+T细胞的特异性抑制效应;过继转移CD4+CD25+T细胞后,观察其对小鼠动脉粥样斑块形成的影响。结果阿司匹林处理的树突状细胞共刺激分子CDSO和CD86表达减少,形态学表现为未成熟树突状细胞;未成熟树突状细胞比成熟树突状细胞能诱导更多的特异性CD4+CD25+T细胞,培养体系中IL-10和TGF-β1水平明显升高。CD4+CD25+T细胞体外明显抑制效应性T细胞的增殖以及IFN-γ的分泌。体内,过继转移HSP60特异性CD4+CD25+T细胞组小鼠动脉粥样斑块面积显著小于对照组。结论未成熟树突状细胞可诱导出HSP60抗原特异性CD4+CD25+ T细胞,后者在体内能明显抑制动脉粥样斑块的形成。

Objective To explore the induction of antigen-specific-CD4^＋CD25^＋ T cell in vitro and its effect on the formation of atherosclerotic plaque. Methods Immature dendritic cells were extracted and induced from apoE^-/- mouse bone marrow and then used to induce heat shock protein 60-specific- CD4^＋CD25^＋ T cells in vitro, the frequency of CD4^＋CD25^＋ T cells and IL-10 and TGF-β1 levels in the medium were analysed. Mixed lymphocyte reactions were used to investigate the inhibitory effect on proliferation and IFN-γ production of effector T cells. After infusing the CD4^＋CD25^＋ T cells into homogenous apoE^-/- mice, 8 weeks later, the size of atherosclerotic plaques was meassured. Results Compared with the control group, the expression of co-stimulating factor CD80, CD86 on aspirin-treated dendritic cells was down-regulated. Immature dendritic cells induced more anti- gen-specific-CD4^＋CD25^＋ T cells than the mature ones and IL-10 and TGF-β1 levels in the culture medium were higher. These CD4^＋CD25^＋ T cells significantly suppressed the proliferation and the IFN-γ production of effector T cells in vitro. The atherosclerotic plaques in the CD4^＋CD25^＋ T cells treated mice were smaller than untreated animals. Conclusion Immature dendritic cells can be used to induce HSP60 antigen-specific-CD4^＋CD25^＋ T cells in vitro and the later can inhibit the progression of atheroscleresis.