热休克蛋白60口服耐受诱导特异性调节T细胞对动脉粥样硬化斑块的影响

目的 探讨热休克蛋白60口服耐受诱导特异性调节T细胞对栽脂蛋白E~(-/-)小鼠动脉粥样硬化宽块形成的影响.方法 8周龄载脂蛋白E~(-/-)小鼠分别口服重组鼠热休克蛋白60-PBS溶液和单纯PBS溶液(对照组),连续5天后高脂饲养12周.比较两组宽块面积;分析脾细胞中CD4~+CD25~+调节性T细胞百分比和功能;酶联免疫吸附法检测上清液细胞因子浓度.结果 与对照组比较,口服热休克蛋白60组斑块面积显著减小,脾细胞中CD4~+CD25~+调节性T细胞百分比显著升高,CD4~+CD25~+调节性T细胞增殖反应下降,上清液中转化生长因子β和白细胞介素10浓度显著升高,而γ干扰素浓度显著下降.结论 热休克蛋白60口服耐受能诱导CD4~+CD25~+调节性T细胞介导抗原特异性免疫耐受;口服热休克蛋白60可能会抑制小鼠动脉粥样硬化斑块的形成.

Effect of Oral Tolerance to HSP60 Inducing Antigen-Specific T Cells on the Formation of Atherosclerotic Plaque in Mouse

Aim To evaluate whether heat shock protein 60 (HSP60) oral administration could induce antigen-specific CD4~+ CD25~+ regulatory T cells and its effect on the formation of atherosclerotic plaque in hypercholesterolemic ape-lipeprotein (Ape) E~(-/-) mice.Methods At 8 weeks of age,12 male Ape E~(-/-) mice were divided into two groups that were orally administrated PBS plus HSP60 and only PBS separately for 5 days,and a high-cholesterol diet was started 5 days after the last treatment for 12 weeks,at which time pathological analysis of plaque was performed,percentage of CD4~+ CD25~+ regulatory T cella in splenocytes were analyzed by FCAS,proliferation response of splenocytes to HSP60 was detected and cytokines in the superanant were determined by ELISA.Results Compared with control animals,oral tolerance to HSP60 resulted in a significant decrease in the size of atherosclerotic plaques,and had a significant increase in CD4~+ CD25~+ regulatory T cells in spleen.Speeifical proliferation response of CD4~+ CD25~+ regulatory T cells in spleno-cytes to HSP60 was significantly suppressed and the level of TGF-β and IL-10 in the superanant increased while IFN-γ de-creased significantly.Conclusion HSP60 oral tolerance can induce antigen-specific CD4~+ CD25~+ regulatory T cells which in turn attenuates the progression of atherosclerotic plaque.This provides a new immunologic approach for the pre-vention of atherosclerosis.