Smith D A, Bickle Q D, Kaye P M
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.
Immunology. 1994 Jul;82(3):419-26.
Treatment of mice with the benzodiazepine derivative Ro11-3128 1-2 days post-infection with Schistosoma mansoni leads to arrest of virtually all schistosomula at the skin stage, and results in the development of protective immunity to challenge infection. A characteristic feature of Ro11-3128 treatment in vitro is the formation of exudates and membranous blebs at the schistosomular surface; other drugs tested, such as Ro15-5458 and oxamniquine which are also effective against the skin stages but relatively ineffective in inducing protection, do not induce this reaction. Here, we have examined whether such in vitro treatment causes enhanced presentation of schistosomular antigens by host antigen-presenting cells (APC) using an in vitro assay with activated peritoneal adherent cells as APC and T cells from S. mansoni antigen-sensitized mice. We have shown that viable mechanically transformed schistosomula (MS) can be processed and presented with similar kinetics to soluble antigen. However, in vitro drug treatment leads to enhanced presentation of MS. Experiments in which membranous blebs and antigen released by Ro11-3128-treated parasites during in vitro culture were separated from the remaining intact schistosomula, demonstrated significant stimulatory activity in the soluble and particulate-released antigen fractions. Filtration, antigen transfer experiments and SDS-PAGE analysis of the released material further suggested that most of the activity resided in the particulate fraction. Thus, quantitative and qualitative changes to antigen presentation by Ro11-3128 treatment early after infection may underlie the immunoprotective efficacy of Ro11-3128-abbreviated infections.
在用曼氏血吸虫感染小鼠1 - 2天后，用苯二氮䓬衍生物Ro11 - 3128进行治疗，几乎可使所有皮肤期的血吸虫童虫停滞，并产生针对攻击感染的保护性免疫。Ro11 - 3128体外治疗的一个特征是在血吸虫童虫表面形成渗出物和膜泡；所测试的其他药物，如Ro15 - 5458和奥沙尼喹，虽然对皮肤期也有效，但在诱导保护方面相对无效，不会引发这种反应。在此，我们使用以活化的腹腔黏附细胞作为抗原呈递细胞（APC）以及来自曼氏血吸虫抗原致敏小鼠的T细胞的体外试验，研究了这种体外治疗是否会导致宿主抗原呈递细胞增强对血吸虫童虫抗原的呈递。我们已经表明，活的经机械转化的血吸虫童虫（MS）能够被处理，并以与可溶性抗原相似的动力学进行呈递。然而，体外药物治疗会导致MS的呈递增强。在体外培养期间，将Ro11 - 3128处理的寄生虫释放的膜泡和抗原与其余完整的血吸虫童虫分离的实验表明，可溶性和颗粒释放的抗原部分具有显著的刺激活性。对释放物质的过滤、抗原转移实验和SDS - PAGE分析进一步表明，大部分活性存在于颗粒部分。因此，感染后早期用Ro11 - 3128治疗对抗原呈递的定量和定性变化可能是Ro11 - 3128缩短感染的免疫保护功效的基础。
