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.