Plumas-Marty B, Taibi A, Pessoa H, Verwaerde C, Loyens M, Pommier V, Velge P, Capron A, Ouaïssi A
Centre d'Immunologie et de Biologie parasitaire, Unité Mixte INSERM U.167 CNRS 624, Institut Pasteur, Lille, France.
Res Immunol. 1993 Oct;144(8):553-63. doi: 10.1016/s0923-2494(05)80002-1.
Three Trypanosoma cruzi glutathione-binding proteins (TcGBP) of 45, 30 and 25 kDa presenting glutathione S transferase activity were characterized from T. cruzi epimastigotes. We show here that immunization of mice using TcGBP and complete Freund's adjuvant (CFA) did not protect the animals against a challenge with bloodstream trypomastigotes. In contrast, immunization of mice using TcGBP in association with Bordetella pertussis plus alum (BpAI) resulted in greatly diminished parasitaemia and significantly protected the animals from lethal infection. Using TcGBP mixed with BpAI and a lower challenge dose, we obtained strongly diminished parasitaemia and 100% protection in terms of survival. Only sera from mice immunized with TcGBP plus BpAI were able to kill trypomastigotes by complement-mediated lysis, whereas sera from mice immunized with TcGBP plus CFA did not. Interestingly, sera from mice immunized with TcGBP plus BpAI showed significant levels of specific IgE, IgG2a and IgG2b antibodies, whereas these isotypes were not detected in sera from mice immunized with TcGBP in CFA. All these levels were increased in sera of protected animals. These results demonstrate that TcGBP antigens can confer resistance to T. cruzi acute infection in mice, and suggest a possible functional role for both IgE and IgG2 isotypes in the induction of protective immunity.
从克氏锥虫前鞭毛体中鉴定出三种具有谷胱甘肽S转移酶活性、分子量分别为45 kDa、30 kDa和25 kDa的克氏锥虫谷胱甘肽结合蛋白(TcGBP)。我们在此表明,用TcGBP和完全弗氏佐剂(CFA)免疫小鼠并不能保护动物免受血流型锥鞭毛体的攻击。相反,用TcGBP联合百日咳博德特氏菌加明矾(BpAI)免疫小鼠可使寄生虫血症大大减轻,并显著保护动物免受致命感染。使用与BpAI混合的TcGBP和较低的攻击剂量,我们在生存方面获得了寄生虫血症大幅降低和100%的保护率。只有用TcGBP加BpAI免疫的小鼠血清能够通过补体介导的裂解作用杀死锥鞭毛体,而用TcGBP加CFA免疫的小鼠血清则不能。有趣的是,用TcGBP加BpAI免疫的小鼠血清显示出显著水平的特异性IgE、IgG2a和IgG2b抗体,而在用CFA中TcGBP免疫的小鼠血清中未检测到这些同种型。在受保护动物的血清中,所有这些水平都有所升高。这些结果表明,TcGBP抗原可使小鼠对克氏锥虫急性感染产生抗性,并提示IgE和IgG2同种型在诱导保护性免疫中可能具有功能性作用。