Interleukin-12 and protective immunity to schistosomes.

The attenuated vaccine against Schistosoma mansoni induces Th1-mediated protective immunity and we have sought to identify a role for IL-12 in this model. Elevated levels of IL-12 (p40 mRNA) were detected in the lymph nodes (LN) and the lungs of vaccinated mice, whilst treatment of vaccinated mice with anti-IL-12 antibodies decreased the ratio of IFN gamma:IL-4 secreted by in vitro-cultured LN cells. However, there was only marginal abrogation of the level of resistance in these mice. Soluble antigens from the lung-stage of the parasite (SLAP) appeared to be efficient stimulators of IFN gamma and IL-12 secretion. These antigens when used to immunise mice in conjunction with IL-12 as an adjuvant, elicited a polarised Th1 response with abundant IFN gamma secretion but no IL-4. This immunisation regime also induced significant protection against reinfection, whereas inoculation of mice with SLAP alone did not. The induction of a dominant Th1 response using SLAP + IL-12 probably operates via IFN gamma production by natural killer (NK) cells stimulated by IL-12, since in vivo ablation of NK cells using anti-NK1.1 antibody reduced CD4(+)-dependent IFN gamma production from cultured LN cells by over 97%. Nevertheless, in mice with a genetic disruption of the IFN gamma receptor, administration of SLAP + IL-12 induced levels of IFN gamma equal to those in wild-type mice, thus showing that in this model IL-12 can directly prime T cells independent of IFN gamma. Clearly, IL-12 has a critical role in protective immunity to schistosomes and it may aid the development of an effective vaccine against this disease.