RESISTANCE INDUCED BY DRUG ABBREVIATED SCHISTOSOMA-MANSONI INFECTIONS- TREATMENT WITH THE DRUG RO11-3128 LEADS TO ENHANCED ANTIGEN PRESENTATION

Treatment of mice with the benzodiazepine derivative Ro11-3128 1-2 day s post-infection with Schistosoma mansoni leads to arrest of virtually all schistosomula at the skin stage, and results in the development o f protective immunity to challenge infection. A characteristic feature of Ro11-3128 treatment in vitro is the formation of exudates and memb ranous blebs at the schistosomular surface; other drugs tested, such a s Ro15-5458 and oxamniquine which are also effective against the skin stages but relatively ineffective in inducing protection, do not induc e this reaction. Here, we have examined whether such in vitro treatmen t causes enhanced presentation of schistosomular antigens by host anti gen-presenting cells (APC) using an in vitro assay with activated peri toneal adherent cells as APC and T cells from S. mansoni antigen-sensi tized mice. We have shown that viable mechanically transformed schisto somula (MS) can be processed and presented with similar kinetics to so luble antigen. However, in vitro drug treatment leads to enhanced pres entation of MS. Experiments in which membranous blebs and antigen rele ased by Ro11-3128-treated parasites during in vitro culture were separ ated from the remaining intact schistosomula, demonstrated significant stimulatory activity in the soluble and particulate-released antigen fractions. Filtration, antigen transfer experiments and SDS-PAGE analy sis of the released material further suggested that most of the activi ty resided in the particulate fraction. Thus, quantitative and qualita tive changes to antigen presentation by Ro11-3128 treatment early afte r infection may underlie the immunoprotective efficacy of Ro11-3128-ab breviated infections.