摘要
目的:探讨体外CD134L单抗或CTLA4Ig对狼疮样BXSB小鼠脾细胞分泌IL-6、IFN-γ及自身抗体的影响。方法:采用未经治疗的狼疮样BXSB小鼠模型,应用CD134L单抗和/或CTLA4Ig体外特异性阻断CD134-CD134L或B7-CD28通路后,用MTT法测定分裂原刀豆蛋白A(ConA)诱导的脾淋巴细胞增殖反应和用ELISA方法测定ConA诱导的脾细胞培养上清液中IL-6、IFN-γ和抗ds-DNA抗体的表达水平,并与经中药狼疮方或强的松治疗的狼疮样BXSB小鼠模型进行比较。结果: (1)在单纯培养或经ConA刺激后培养,相比于正常对照鼠,狼疮样小鼠脾淋巴细胞都表现有增殖反应性的显著增高,IFN-γ、 IL-6蛋白量的增高和抗ds-DNA抗体的过度分泌。(2)经强的松或中药狼疮方体内治疗后,狼疮样小鼠脾淋巴细胞体外培养的增殖反应性及IFN-γ、IL-6的分泌都受到明显抑制,抗ds-DNA抗体的产生也明显减少。(3)体外单独应用CD134L单抗或 CTLA4Ig特异性阻断CD134-CD134L或B7-CD28共刺激信号通路,同样可以显著抑制体外培养的狼疮样小鼠脾淋巴细胞的增殖反应及IFN-γ、IL-6的分泌,并可明显减少抗ds-DNA抗体的产生,但它们的抑制作用比强的松、中药狼疮方体内治疗狼疮样小鼠时所表现出的类似效应要弱。(4)联合CD134L单抗和CTLA4Ig,则治疗作用显著提高,其抑制脾淋巴细胞的增殖反应及 IFN-γ、IL-6的分泌,抗ds-DNA抗体产生的作用都优于中药狼疮方的体内治疗效果,而与强的松的体内治疗效应相当。结论: CD134-CD134L可以提供独立的、非B7-CD28依赖的,另一种驱动抗原特异性T细胞增殖的协同刺激通路。同时阻断B7与 CD28、CD134L与CD134间的相互作用,使自身反应性T淋巴细胞的活化和增殖受到快速而最大限度的抑制,对治疗SLE等自身免疫性疾病可能是一种较理想的免疫干预模式。
Objective：To investigate the effect of anti-CD134 mAb or CTLA4Ig on ConA induced splenic cell proliferation,Th eytoldne secretion and production of anti-dsDNA antibody from splenic lymphtoeyte in vitro in lupus-prone BXSB mice. Methods： Eighteen male lupus-prone BXSB mice model and 6 syngeneie normal C57BL/6 male mice were used in the experiment. The model mice were divided into three groups：un-treated group, Lupus recipe （LR） treated group and prednisone （pred.） treated group. The miee＇s splenic cell suspension from above groups was euhure stimulated by ConA respectively. The splenic cells from un-treated model mice were further divided into Anti-CD134L mAb,CTLA4Ig or Anti-CD134L mAb ＋ CTLA4Ig treated subgroups. The ConA induced splenic cell proliferation was measured by MTT colorimetric assay. The levels of IFN-γ, IL-6 and anti-dsDNA antibody in cell supematant were measured by ELISA. Results： （1）The splenic cell proliferative reaction and contents of IFN-3t, IL-6 and anti-dsDNA antibody in cell supematant of either spontaneous or ConA induced culture in the un-treated model group were obviously higher than that of the normal control or other groups. （2） The splenic cell proliferative reaction and production of IFN-γ, IL-6 and anti-dsDNA antibody in the CD134L/CTLA4Ig treated group, LR treated goup or pred. treated group was not different from the normal control significandy. （3）To compared with CD134L treated group or CTLA4Ig treated gruop, the CD134L/CTLA4Ig and prednisone reduced significandy the splenic cell proliferative reaction and production of IFN-γ,IL-6 and anti-dsDNA antibody in cell supematant of either spontaneous or ConA induced culture,while no difference was found between CD134L treated group and CTLA4Ig treated proup. Conclusion：The lupus-prone BXSB mice might present abnormal lymphocyte proliferation ,spontaneously express cytokines and secrete high level of autoantibody during tho SLE development. LR and corticosteroids could obviously inhibit the abnormal lymphocyte proliferation;reduce the Th eytokineformation and antoantibedy production Blockade of CD134-CD134L or B7-CD28 costimulatory pathway by Anti-CD134L mAb or CT- LA41g could inhibit the activation of T cells and B cells like LR and eortieosteroids. Furthermore, by blockade of both CD134-CD134L and CD28-B7 pathways, the frequency of alloreaetive Teel was markedly reduced and was maintained at low levels so as to treat SLE effectively.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2006年第1期44-48,共5页
Chinese Journal of Immunology
基金
中山医科大学211工程重点科研基金资助项目(98151)
