SummaryIn the mouse, infection withSchistosoma mansoni results in an egg-producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence ofegg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL5) production by T cells from infected mice and interferon y (IFN-y) synthesis bycells from vaccinated animals (7), suggested differential CD4+ subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-y and IL-2 (secreted by Thl cells) as compared with IL4 and 11,5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Thl lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Thl reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Thl responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Thl function accompanied by a coincident expression of Th2 responses . Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Thl function. This previously unrecognized downregulation of Thl cytokine production may be an important immunological consequence of helminth infection related to host adaptation.

The complementary DNA sequence encoding the Mr 28,000 antigen of Schistosoma mansoni has been isolated and expressed in Escherichia coli. Experimental vaccination of rats, hamsters and monkeys with a recombinant fusion protein induces a strongly cytotoxic antibody response. Immunization of rats and hamsters with this protein leads to significant protection against a natural challenge infection with live cercariae.

SUMMARYA total of 129 children were treated forSchistosoma mansoniinfections, and followed for intensity of reinfection at3-monthly intervals over a 21-month period. Blood samples were taken before treatment and at 5 weeks and 6, 12 and 18 months after treatment. This paper presents a statistical analysis of the relationship between various immune responses and subsequent reinfection. Responses analysed were: blood eosinophil levels; IgE antibodies against schistosomulum antigens; IgG antibodies mediating eosinophil-dependent killing of schistosomula; antibodies inhibiting the binding to schistosomulum antigens of two rat monoclonal antibodies that also recognize egg antigens; the levels of anti-adult worm and of anti-egg (total, IgM and IgG) antibodies; and IgM anti-schistosomulum antibodies. Results for each assay were well correlated for each of the five separate blood samples. None of the assays were predictive of resistance to reinfection, butsusceptibilityto reinfection was strongly correlated with results in the preceding blood samples for total anti-egg antibodies and the inhibition of binding of one of the two monoclonal antibodies. Further analysis also revealed a correlation between reinfection intensities and both IgM anti-schistosomulum antibodies and IgM and IgG anti-egg antibodies. These results are consistent with the hypothesis that early infections elicit the development, in response to egg antigens, of antibodies that block immune mechanisms directed against schistosomula. Blocking antibodies may be IgM, but might also be of an ineffective IgG isotype. The existence of such antibodies in young children would explain the slow development of immunity in the face of a range of detectable, potentially protective immune responses.