摘要
目的 联合应用抗B7分子的单克隆抗体 (单抗 )体外诱导T细胞免疫耐受模型 ,并探讨B7分子在T细胞免疫耐受中的作用及其机制。方法 体外联合应用抗B7单抗诱导T细胞免疫耐受 ,3H TdR掺入法检测T细胞增殖 ,逆转录 聚合酶链反应 (RT PCR)检测T细胞细胞因子mRNA合成。为了排除其它粘附分子的作用 ,应用联合转染DR7或 (和 )B7分子基因的CHO细胞系作为人工抗原递呈细胞 (APC)介导混合淋巴细胞反应 (MLR)。结果 T细胞增殖实验显示 ,B7 1(CD80 )和B7 2 (CD86 )单抗单独应用可以部分阻断MLR ,其中CD86 单抗的阻断作用更为明显。两种抗体联合应用时 ,可以明显阻断MLR。RT PCR显示 :应用抗B7单抗联合阻断后 2 4h ,IFN γ及IL 2mRNA合成明显减少 ,而IL 4mRNA合成较前明显增加。人工APC介导的MLR显示 ,仅有第一信号 (DR7)时也可以使T细胞增殖 ,但需要达到一定的信号强度 ;给予DR7信号同时给予共刺激信号CD80 可以增强T细胞反应 ,增强效应可以被抗CD80 单抗所阻断。结论 B7分子在T细胞免疫反应中具有重要的作用 ,可以非特异性增强T细胞免疫反应。阻断B7 CD2 8信号传导通路 ,可以诱导T细胞免疫耐受形成 ,其中CD86 分子的作用可能更为重要。抗B7单抗诱导的T细胞无反应性后 ,向Th2方向分化 。
Objective To explore the role and mechanism of B7 molecules in T cell anergy. Methods Anti B7 1(CD 80 ) and anti B7 2(CD 86 ) monoclonal antibodies were used to induce T cell anergy. T cell proliferation were assayed by mixed lymphocyte reaction(MLR) with 3H TdR incorporation, and cytokine mRNA transcripts were analyzed with reverse transcriptase polymerase chain reaction (RT PCR). B7 transfected CHO cells were used as artificial antigen presentation cells (APCs) in MLR to exclude the effects of other costimulatory molecules. Results MLR results showed that the proliferation of T cells was inhibited to various extents by anti CD 80 or anti CD 86 monoclonal antibody, the effect of anti CD 86 antibody was greater than that of anti CD 80 antibody, and the proliferation was totally blocked when the two were used together. The results of RT PCR demonstrated that IL 2 and IFN γ mRNA transcripts decreased whereas IL 4 mRNA transcripts increased in T cell after treatment with anti B7 antibo dies for 24 hours. In MLR with artificial APC, signal one (DR7) alone could stimulate T cell proliferation at a certain threshold intensity. Costimulator B7 1 molecule could help signal one in T cell proliferation. This effect was blocked by anti CD 80 . Conclusion B7 molecules play an important role in T cell immune response. Blockade of B7 family resulted in T cell anergy. The role of CD 86 may be more important than that of CD 80 . The conversion of cytokine profile from Th1's to Th2's reflected that anergetic T cells were differentiated into Th2 cells by anti B7 suggesting that anergetic blockade of costimulator molecules may be one of the mechanisms of T cell.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2002年第7期341-344,共4页
Chinese Journal of Hematology
基金
国家自然科学基金资助项目 (3 9770 3 2 8)
