霉酚酸及其衍生物对人T淋巴细胞及混合淋巴细胞免疫应答的影响  

Effects of mycophenolate acid and its derivatives on human T-cells and mixed leukocytes

作　　者：孙怡[1] 杨滨燕[1] 王慧[1] 吴长有[1] 

机构地区：[1]中山大学中山医学院免疫研究所热带传染病教育部重点实验室,广州510080

出　　处：《免疫学杂志》2013年第1期1-8,共8页Immunological Journal

摘　　要：目的探讨霉酚酸及霉酚酸衍生物对人T淋巴细胞和混合淋巴细胞免疫应答的影响。方法从正常人外周血中分离单个核淋巴细胞(PBMC),在抗CD3刺激下和混合淋巴细胞反应体系中,加入或不加霉酚酸及其衍生物共培养,应用ELISA和流式细胞术检测CD4+和CD8+T细胞细胞因子的产生、细胞活化和增殖情况。结果经抗CD3刺激后,PBMC产生的细胞因子明显增加,加入霉酚酸及其衍生物后,IFN-γ及TNF-α明显降低,IL-2产生略有增加。在混和淋巴细胞反应体系中,3种细胞因子产生皆被抑制。抗CD3刺激和混和淋巴细胞反应后,T细胞表面活化分子CD25及CD69表达增加,加入霉酚酸及其衍生物共培养24、48 h后,T细胞CD25及CD69的表达并未被抑制。霉酚酸及其衍生物可抑制抗CD3刺激下和混和淋巴细胞反应后T细胞的增殖。结论霉酚酸及其衍生物对T淋巴细胞和混合淋巴细胞体系中因子的产生和细胞增殖都有抑制作用,为其在临床自身免疫疾病及移植排斥中的广泛应用提供了理论依据。Mycophenolate acid （MPA）, a kind of immunosuppressive medications, plays an important role in autoimmune diseases and transplantation. In this study, we aimed to investigate the effects of MPA and its derivatives on the T cell immune response after stimulation with anti-CD3 or mixed leukocytes reaction （MLR）. PBMCs obtained from healthy donors were cultured with anti-CD3 or with MLR system in the presence or absence of MPA and its derivatives. The level of IFN-γ TNF-α, and IL-2 from PBMCs was detected by ELISA, while the level of T cell proliferation and CD25/CD69 expressions were analyzed by flow cytometry. The derivatives of MPA inhibited significantly the production of IFN-γ and TNF-α, but slightly promoted IL-2 production from PBMCs induced by anti-CD3; While in MLR system, the production of all the three cytokines were suppressed. We could find the same result when added the two derivatives of MPA at different time points. Furthermore, the derivatives displayed no effect on the expression of CD25 and CD69, but inhibited the proliferation of T cells at the concentration of 10^-5 mol/L after incubation for 2-3 d, as compared with positive control group. Our result demonstrated that MPA and its derivatives can inhibit the immunologic functions of activated human T cell and mixed leukocytes.

关 键 词：霉酚酸 T细胞 混合淋巴细胞培养 细胞增殖 细胞因子 

分 类 号：R392.11[医药卫生—免疫学]