【作者】 姜山；

【导师】 谭锦泉； 张秋萍；

【作者基本信息】 安徽医科大学 ， 免疫学， 2004， 硕士

【摘要】 目的：了解Ⅰ型变态反应性疾病中CD4~+ CD25~+调节性T细胞的变化及其意义，探讨Ⅰ型变态反应性疾病的发生机制，为Ⅰ型变态反应性疾病的治疗提供新方法和新思路。方法：使用免疫磁珠分选正常对照组和Ⅰ型变态反应性疾病患者的CD4~+CD25~+调节性T细胞；流式细胞仪分析其表型及其在外周血单个核细胞中的比例；分别用变应原或联合应用抗CD3单抗和抗CD28单抗，刺激来源于正常对照组和患者的CD4~+CD25~+调节性T细胞和CD4~+CD25~-T细胞，ELISA、3H-TdR等检测CD4~+CD25~+调节性T细胞功能。结果：(1)在正常人体内CD4~+CD25~+调节性T细胞能抑制变应原对CD4~+CD25~-T细胞的刺激增殖反应和细胞因子分泌。(2)来源于Ⅰ型变态反应性疾病患者的CD4~+CD25~-T细胞在变应原的刺激下主要分泌Th2型细胞因子，如IL-5、IL-10和IL-13等，而不分泌Th1型细胞因子，如IFN-γ。(3)在数量上，患者体内的CD4~+CD25~+调节性T细胞与正常对照组相比无显著差异。(4)在功能上，患者体内的CD4~+CD25~+调节性T细胞对变应原或联合应用抗CD3单抗和抗CD28单抗的刺激不表现出增殖反应。所以在患者体内CD4~+CD25~+调节性T细胞仍然和正常个体一样具有免疫无能性。(5)在免疫抑制功能上，CD4~+CD25~+调节性T细胞却不能抑制变应原对CD4~+CD25~-T细胞的活化，而能抑制抗CD3和抗CD28单抗对CD4~+CD25~-T细胞的刺激作用。(6)抗-GITR抗体能明显降低CD4~+CD25~+调节性T细胞的免疫抑制功能。结论：(1)CD4~+CD25~+调节性T细胞参与了机体对变应原的免疫反应，在变态反应性疾病的发生发展中有着重要的作用。(2)Ⅰ型变态反应性疾病患者体内的CD4~+CD25~+调节性T细胞可能存在某种功能性缺陷。(3)CD4~+CD25~+调节性T细胞膜上的GITR可能参与了该细胞对变应原刺激的抑制过程。更多还原

【Abstract】 Objective: To investigate the changes of CD4+CD25+ regulatory T cells in type I Allergic diseases, and to explore the mechanism of allergy. Give new approach of treat. Methods: CD4+ T cells were isolated by Dynabeads M-450 from PBMC, CD25+ Microbeads isolated CD4+CD25+ regulatory T cells from CD4+T cells. Phenotype of the T cell lines was detemined by Flow cytometry. In the presence of allergen or anti-CD3 mAb and anti-CD28 mAb, we studied the function of CD4+ CD25+ regulatory T cells isolated from non-allergy donors and allergy donors. ELISA and 3H-TdR were used to investigate the function of CD4+CD25+ regulatory T cells. Results: DThese results show that CD4+ CD25+ regulatory T cells from non-allergy donors can inhibit CD4+CD25" T cells activation and the production of cytokines. Din presence of allergen, Th2 cytokines were secreted by CD4+ CD25" T in allergy, such as IL-5, IL-10 and IL-13, not Thl cytokines, such as IFN- . The number of CD4+CD25+ regulatory T cells has no significantly difference between non-allergy donors and allergy donors. In function, CD4+ CD25+ regulatory T cells from non-allergy donors and allergy donors don’t proliferate in the presence of allgern or anti-CD3 mAb and anti-CD28 mAb. It is only in the presence of allergen that CD4+ CD25+ regulatory T cells secrete IL-10. So, these regulatory T cells still are in anergic. But inhibition of proliferation by CD4+CD25+ regulatory T cells from allergy donors was significantly reduced under the stimulation of allgen, not anti-CD3 mAb and anti-CD28 mAb. D Suppression of allergen-driven T cell proliferation by CD4+CD25+ regulatory T cells was reversed by antibody to glucocorticoid-induced TNF receptor (GITR), but this did not reverse suppression of cytokine production. Conclusion: DCD4+CD25+regulatory T involved in the immune response to allergen in human. It play a crucial role in the development of allergy. CD4+CD25+ regulatory T in type allergic diseases donors may have defect in the function of CD4+CD25+ regulatory T cells. GITR can involved in the process ofinhibition of CD4+CD25+ regulatory T cells.更多还原