阻断型CD154抗体和CD80抗体生物学作用的研究

Study on the biological activities of the blocking effects of anti-CD154 and anti-CD80 monoclonal antibodies

为比较阻断型抗人CD154单克隆抗体(1B1)和抗人CD80单克隆抗体(3H8)的单独及联合应用在调节CD4+T细胞对同种抗原的初次和再次免疫应答中的作用。采用免疫磁珠阴性选择法分离获得人外周血CD4+T细胞、将纯化的CD4+T细胞与刺激细胞体外共培养,通过检测培养上清IL-2、IFN-γ水平以及CD4+T细胞的增殖来评价1B1和3H8的生物学作用。结果显示,1B1和3H8单独或联合应用能不同程度地抑制混合淋巴细胞反应中CD4+T细胞对同种抗原刺激的增殖,下调CD4+T细胞分泌IL-2和IFN-γ,并且在再次反应中能有效诱导CD4+T细胞对同种抗原的免疫低反应性。因此,1B1和3H8的单独及联合应用在移植排斥的免疫干预及同种抗原免疫耐受的诱导中具有潜在的应用前景。

To evaluate the biological effects of anti-CD154 and anti-CD80 monoclonal antibodies alone or in combination to modulate the primary and secondary immune responses of CD4^＋ T cells against the allo-antigens, functional anti-CD154 and/or anti-CD80 mAb were employed in the ex vivo mixed lymphocyte reaction （MLR）. The cytokine levels of IL-2 and IFN-γ in the supernatants of MLR cultures were detected by ELISA. On the basis of cytokine detection and the results of MLR assay, it was evidenced that monoclonal antibodies 1B1 and 3H8 alone or in combination could inhibit the proliferation of CD4^＋ T cells upon the stimulation with allo-antigens in primary MLR at different extents, and induced effectively hyporesponsiveness of immune responses upon allo- antigens stimulation in the secondary MLR. Moreover, these monoclonal antibodies could minimize the secretions of IL-2 and IFN-γ from CD4^＋T cells. These results indicate that the applications of monoclonal antibodies 1B1 and 3H8 alone or in combination may show their potential usages to induce immuno-tolerance against allo-antigens or to prevent allograft rejections.