共刺激分子CD80和CD86在蠕虫保护性免疫及其Th_2免疫应答中作用机制的研究

Effect of CD80and CD86on the protection from and Th_2 immune response to helminth infection

目的:探讨共刺激分子CD80和CD86在蠕虫保护性免疫及其Th2免疫应答中的作用机制。方法:采用巴西日圆线虫第3期幼虫感染BALB/c小鼠,在感染当天、感染后第3、7d分别腹腔注射大鼠抗CD80和/或抗CD86单克隆抗体,以阻断协同刺激信号。在感染当天,感染后第7、14d,计数小鼠外周血液的嗜酸性粒细胞,于感染后第14d计数小肠绒毛嗜酸性粒细胞;采用WatanabeN法测定IgE。结果:联合应用抗CD80和抗CD86两种单克隆抗体可导致成虫产卵量明显增加,成虫数量显著增多及排虫时间延迟。同时两种单克隆抗体也完全抑制了外周血液及小肠组织的嗜酸性粒细胞的增多并部分抑制了IgE水平的升高。而单独应用抗CD80或抗CD86McAb对保护性免疫及Th2型免疫应答反应均无明显影响。结论:在蠕虫保护性免疫和Th2型免疫应答反应中,T细胞的活化需要CD80和CD86两种共刺激分子的参与;而CD80或CD86单一刺激分子即可提供足够的共刺激信号。研究提示,人为调控CD80和CD86共刺激分子可能有助于对蠕虫病及Th2型免疫应答所介导的其它疾病的治疗。

Objective:To explore the effect of the constimulatory molecules CD80and CD86on the worm immune response to helminth infection.Methods:To obstruct constimulatory signal,BALB/c mice infected with Nipponstrongylus brasiliensis(Nb)LⅢwere treated with anti-CD80and/or anti-CD86monoclonal antibodies on days0,3and7.After infection,eosinophils of mice were counted on days0,7and14in peripheral blood and on day14in small intestine.IgE was detected by Watanabe N ELISA method.Re sults:Combined treatment with anti-CD80and anti-CD86enhanced the number of adults and eggs obviously and defered the course of discharging adult worms.Furthermore,the two monoclonal antibodies completely inhibited Nb-induced eosinophil both in the blood and in the small intestine and partly suppressed IgE production.However,administration of either anti-CD80or anti-CD86alone had little effect on eosinophil and on the elevation of IgE levels.Conclusion:CD80and CD86costimulation is required during a Th2immune response to Nipponstrongylus brasiliensis and ei-ther CD80or CD86can provide a sufficient costimulatory signal that lead s to T cell activation and differentiation of function.