Velge-Roussel F, Auriault C, Damonneville M, Capron A
Centre d'Immunologie et de Biologie Parasitaire, Unité mixte INSERM U 167-CNRS 624, Institut Pasteur, Lille, France.
J Immunol. 1991 Dec 1;147(11):3967-72.
In our previous work on the idiotypic network in the rat model of schistosomiasis we showed that immunization with an IgE mAb specific for 26/56-kDa parasitic Ag resulted in the production of anti-anti-Id antibodies of both the IgG and IgE classes. Further studies demonstrated that anti-Ab2 T cell lines, obtained by immunization with Ab2 antibodies, functioned as conventional Th cells; they were MHC-restricted and required APC to proliferate in the presence of the native schistosomula Ag and the Ab2 antibodies. We report the involvement of these anti-Ab2 cells in the regulation of protective immunity. The transfer of long term culture anti-Ab2 T cell lines into LOU/M rats, followed by a challenge infection by Schistosoma mansoni 1 day after the cell transfer led to a slight increase in the worm burden. On the contrary, the transfer of anti-Ab2 T cells 90 days before S. mansoni infection induced a significant reduction of the worm burden (up to 57%). T cells recovered from the protected rats were stimulated by the native schistosomula Ag as well as by tryptic fragments of IgG isolated from the Ab2 sera, in the presence of irradiated thymic cells as APC. We also analyzed the humoral response developed by the rats after transfer with the anti-Ab2 T cell lines. The sera induced various inflammatory cells into cytotoxic effectors against the larvae of S. mansoni, arguing for the presence of functional IgE in the sera. Moreover, when these sera were passively transferred into rats infected 1 day later, a significant reduction of the worm burden was observed. However, antibody-dependent cytotoxic mechanisms efficient 10 days after the anti-Ab2 T cell transfer did not correlate with the protective immunity which required a 90-day delay to be established. These data suggest that the protective immunity induced by the anti-Ab2 cells is supported both by the cellular and humoral components and that in a future vaccinating strategy the idiotypic network may play a crucial role.
在我们先前关于血吸虫病大鼠模型独特型网络的研究中，我们发现用针对26/56-kDa寄生虫抗原的IgE单克隆抗体进行免疫会导致产生IgG和IgE两类抗抗独特型抗体。进一步研究表明，通过用Ab2抗体免疫获得的抗Ab2 T细胞系发挥着传统Th细胞的功能；它们受MHC限制，在存在天然童虫抗原和Ab2抗体的情况下需要抗原呈递细胞才能增殖。我们报告了这些抗Ab2细胞参与保护性免疫的调节。将长期培养的抗Ab2 T细胞系转移到LOU/M大鼠中，在细胞转移1天后用曼氏血吸虫进行攻击感染，导致虫负荷略有增加。相反，在曼氏血吸虫感染前90天转移抗Ab2 T细胞可使虫负荷显著降低（高达57%）。从受保护大鼠中回收的T细胞在存在经辐照的胸腺细胞作为抗原呈递细胞的情况下，受到天然童虫抗原以及从Ab2血清中分离的IgG胰蛋白酶片段的刺激。我们还分析了用抗Ab2 T细胞系转移后大鼠产生的体液反应。这些血清诱导各种炎性细胞成为针对曼氏血吸虫幼虫的细胞毒性效应细胞，这表明血清中存在功能性IgE。此外，当将这些血清被动转移到1天后感染的大鼠中时，观察到虫负荷显著降低。然而，抗Ab2 T细胞转移10天后有效的抗体依赖性细胞毒性机制与需要90天延迟才能建立的保护性免疫无关。这些数据表明，抗Ab2细胞诱导的保护性免疫受到细胞和体液成分的支持，并且在未来的疫苗接种策略中，独特型网络可能发挥关键作用。
