杀伤性人工抗原提呈细胞治疗小鼠皮肤移植排斥及其对治疗鼠整体免疫功能的影响

Killer artificial antigen-presenting cells treating skin allograft rejection and its impact on the overall immune function in mice model

目的:研究杀伤性人工抗原提呈细胞(Ka APC)治疗小鼠皮肤移植排斥的效果及其对治疗鼠整体免疫功能的影响。方法:利用可生物降解的聚乳酸-羟基乙酸共聚物微米球做载体,共价吸附H-2Kb抗原和anti-Fas等负性调节分子,制备针对同种反应性T细胞的特异性Ka APC,治疗以C57BL/6和BALB/c为供受对的小鼠皮肤移植排斥,并利用混合淋巴细胞培养观察治疗鼠对第三方供体的同种反应能力以及通过载瘤实验观察治疗鼠的抗肿瘤能力等,以论证Ka APC治疗对机体整体免疫功能的影响,帮助筛选有效治疗方案。结果:成功制备Ka APC,FACS验证其有正确的表型;Ka APC输注使皮肤移植物的存活时间明显延长,P<0.000 1,但并未显著损伤治疗鼠T细胞对第三方供体鼠脾细胞的同种增殖能力,也并未显著损伤治疗鼠的抗肿瘤能力。结论:Ka APC可以抑制小鼠皮肤移植排斥并对治疗鼠的整体免疫功能无明显损伤。

Objective： To study the therapeutic effect for skin allograft rejection of killer artificial antigenpresenting cells（ Ka APC） and its impact on the overall immune function in mice model. Methods： Ka APC were prepared by co-coupling H-2Kbantigen and anti-Fas monoclonal antibody onto the biodegradable polylactic-coglycolic acid（ PLGA） microspheres,and then were administered intravenously into BALB / c mice（ H-2Kd） that had previously been grafted with skin squares from C57 BL /6 mice（ H-2Kb）. Tumor cell challenge and third-party mixed lymphocyte culture were used to assess the general immune functions of host. Results： Ka APC microspheres had the correct phenotype as verified by FACS; the skinallograft survival was prolonged significantly（ P〈0. 000 1）after treatment with Ka APC; the proliferation of recipient T cells against the third-party splenocytes and the defense to tumor did not apparently decreased after treatment with Ka APC in therapy mice. Conclusion： The Ka APC have ability to inhibit skin allograft rejection in mice model,without impairment of host overall immune function.