天花粉蛋白抑制T细胞增殖的免疫学机制研究  

A study on the immunological mechanisms underlying the trichosanthin-induced inhibition of T lymphoproliferation

作　　者：王保龙[1] 周芸[1] 江阳[1] 辛利军[1] 周洪[1] 周光炎[1] 

机构地区：[1]上海第二医科大学上海市免疫学研究所,200025

出　　处：《中华微生物学和免疫学杂志》2005年第1期64-68,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学资助项目 (No 3 0 2 71616) ;国家 863资助项目 (2 0 0 1CB5 10 0 0 3 )

摘　　要：目的　研究天花粉蛋白 (Tk)诱导免疫抑制的免疫学机制。方法　应用淋巴细胞体外增殖抑制试验 ,分别对丝裂原ConA、可溶性抗原OVA及CD3联合CD2 8McAb三种T细胞增殖系统进行Tk诱导免疫抑制的剂量依赖性试验。建立OVA特异性的T细胞系 (Tova) ,观察Tk对由IL 2 IL 2R信号介导的T细胞增殖的抑制作用。用FACS测定Tk处理过的脾脏单个核细胞 (SMC)的凋亡。分离骨髓诱导产生未成熟的DC(iBDC) ,比较Tk冲击处理前后DC激活T细胞增殖能力的差异。用Tk冲击处理Tova ,观察Tk冲击处理前后T细胞增殖能力的变化。结果　低剂量的Tk(1ng ml～ 5 0 0ng ml)对OVA增殖系统有强烈的抑制作用 ,对ConA增殖系统抑制较弱 ,而对CD3联合CD2 8McAb及IL 2增殖系统的T细胞增殖几乎无抑制作用。在 5 μg ml的浓度以下 ,Tk不诱导SMC凋亡。Tk冲击处理过的iBDC提呈OVA激活特异性T细胞的能力明显下降 ;而Tk冲击处理过的Tova增殖能力没有受到影响。结论　Tk通过影响APC来诱导免疫抑制。Objective To elucidate the role of APC in the Tk-induced suppression by using animal experimental system. Methods Dose-dependent curves of Tk-induced inhibition of lymphoproliferation to soluble Ag OVA, mitogen ConA, and anti-CD3/CD28 McAbs were determined by in vitro assay. T cells from lymph node of C57BL/6 mice immunized with OVA were subjected to repeat stimulation with OVA to establish OVA-specific T cell lines(Tova). The IL-2-stimulated lymphoproliferation of the mixed T cell line was further examined as a test system to reveal the effect of Tk on the T cells. The possible apoptosis of the splenic mononuclear cells (SMC) induced by Tk was detected by FACS. Furthermore, bone marrow-derived dendritic cells (BDCs) pulse-treated with or without Tk (100 ng/ml) for 12 h were assayed for their APC capabilities of activating Tova. Results Tk of low doses from 1 ng/ml to 500 ng/ml suppressed the lymphoproliferation stimulated by OVA and by ConA. However there was little suppression for IL-2 or for anti-CD3/CD28 McAb-induced lymphoproliferation. Tk did not cause apoptosis of SMC at the concentration less than 5 ng/ml in our experiment. As compared with the control, the lymphoproliferation of Tova to the OVA-pulsed BDCs was remarkably depressed in the presence of Tk. In contrast, the proliferation was not affected when purified Tova was pulsed with Tk alone. Conclusion Tk is active in exerting its effects on APCs for inducing suppression of T responses.

关 键 词：T细胞增殖 处理 免疫学机制 抑制作用 天花粉蛋白 CD28 CD3 丝裂原 特异性 体外增殖 

分 类 号：R285[医药卫生—中药学]