基础医学与临床 ›› 2009, Vol. 29 ›› Issue (6): 618-621.

• 研究论文 • 上一篇    下一篇

不同Aβ多肽与佐剂组合免疫小鼠对Th1/Th2平衡的调节作用

雷甜甜 赵雪梅 梁平   

  1. 中国医学科学院 基础医学研究所 北京协和医学院 基础学院 病理系 中国医学科学院 基础医学研究所 北京协和医学院 基础学院 病理系
  • 收稿日期:2009-03-10 修回日期:2009-04-08 出版日期:2009-06-25 发布日期:2009-06-25
  • 通讯作者: 梁平

Modulation of Th1 and Th2 responses to immunization with different β-amyloid and adjuvant

Tian-tian LEI, Xue-mei ZHAO, Ping LIANG   

  1. Department of Pathology, School of Basic Medicine , IBMS, CAMS&PUMC Department of Pathology, School of Basic Medicine , IBMS, CAMS&PUMC
  • Received:2009-03-10 Revised:2009-04-08 Online:2009-06-25 Published:2009-06-25
  • Contact: Ping LIANG

摘要: 目的 观察野生型和突变型Aβ40及Aβ42与不同佐剂组合对T淋巴细胞亚型的不同刺激和调节作用,以探讨降低Aβ免疫毒性反应的可能途径。方法 BALB/c小鼠随机分组:铝(Al)佐剂对照组、Aβ42+福氏佐剂(CFA)组、Aβ42+Al组、Aβ40+Al组、Aβ40(E22A)+Al组,每组8只。经初次免疫和3次加强免疫,检测抗体效价,培养脾淋巴细胞,分别用各自抗原刺激,48h后用双抗夹心ELISA试剂盒检测培养液中IFN-γ、IL-2、TNF-α和IL-4的含量。72h后用CCK-8法检测脾淋巴细胞特异性增殖反应。结果 经Aβ免疫的4个试验组血清中均有特异性抗Aβ的抗体产生。脾淋巴细胞经各自抗原刺激后,均出现脾淋巴细胞特异性增殖反应。细胞培养上清中细胞因子检测结果显示,Aβ42+CFA组分泌的代表Th1型的细胞因子含量最高,Aβ40(E22A)+Al组则有显著降低(P <0.01)。其中Aβ40及突变型+Al组与Aβ42+Al组相比,分泌的Th1型细胞因子也有明显降低(P<0.05)。结论 Aβ40(E22A)+Al组对T细胞的毒性作用最低,在机体的免疫反应中可能具有更好的安全性。

关键词: 阿尔茨海默病, Aβ多肽, T细胞亚型, 细胞因子

Abstract: Objective To observe stimulation and regulation of T lymphocyte subtypes when using wild-type and mutant Aβ40 and Aβ42 with different adjuvants and to investigate possible ways to lower the toxicity of Aβ immune response. Methods Forty BALB/c mice were randomized into five groups: Al adjuvant group,Aβ42+CFA group,Aβ42+Al group,Aβ40+Al group,Aβ40(E22A)+Al group. After the initial immunization and booster immunization 3 times, antibody titer were detected and the mice were killed. Their splenocytes were stimulated by respective antigen. After 48h quantity of IFN-γ, IL-2, TNF-α and IL-4 were tested. After 72h of culture, the proliferative response of splenocytes were detected by CCK-8 assay. Results Experimental groups generated specific anti-Aβ antibodies and had proliferative response of spleen lymphocytes. Cell culture supernatant of cytokine detection results showed that Aβ42+CFA group had the highest secretion of Th1-type cytokines IFN-γ,IL-2,TNF-α when Aβ40(E22A)+Al group had the lowest.(P <0.01).When Aβ40 and the mutant Aβ40+Al groups compared with Aβ42+Al group, secretion of IFN-γ,IL-2,TNF-α have also decreased significantly(P<0.05).The secretion of IL-4 was no significant difference. Conclusion Aβ40(E22A)+Al group stimulate the lowest toxicity of T cells, and may have better security in the immune response.

Key words: Alzheimer’s disease, Aβ peptide, T cell subtypes, cytokine