Anti-worm antibody specificities in 129/J mice resistant to infection with Schistosoma japonicum. (1984)

Much debate centers on the relevance of the infected mouse as a model for analysis of immunologically-based resistance to reinfection in schistosomiasis mansoni and japonica. One of several unknowns is the relative contribution of classical immunological effector mechanisms compared with manifestations of hepatosplenic disease in expression of resistance to reinfection (Dean et al., 1981, Am. J. trop. Med. Hyg. 30: 113-120). Notwithstanding problems in interpretation of observations on resistance in murine schistosomiasis, it is very clear that the newlytransformed schistosomule is a target of aggressive cytotoxic immune attack at least in vitro (e.g., Smithers and Doenhoff, 1982. In Immunology of parasitic infections, Cohen and Warren (eds.). Blackwell, pp. 527-607). Moreover, there is increasing evidence for an additional phase of of challenge worms in infected mice-i.e., at the postlung, preadult worm stage of development (Smithers and Miller, 1980, Am. J. trop. Med. Hyg. 29: 832-841; Dean et al., 1978, Am. J. trop. Med. Hyg. 27: 957-965; Blum and Cioli, 1981, Parasite Immun. 3: 13-24). It is this phase which is most likely to be influenced by pathology in already-infected, small laboratory rodents (discussed in Damian, 1984, Cont. Topics Immunobiol. 12: 359-420). Previous studies from our laboratories have demonstrated that a high proportion of female 129/J mice exposed percutaneously to 20 to 30 cercariae of Schistosomajaponicum did not contain worms when killed 20 to 50 days later (Mitchell et al., 1981, Int. J. Parasit. 11: 267276; Garcia et al., 1983, J. Parasit. 69: 613-615). In 7 determinations, 11 to 83% (x = 44%) of 129/J mice of various ages were negative for adult worms whereas only 1 of 52 BALB/c mice was not infected. A highly sensitive serological test, based on an anti-worm monoclonal antibody (Mitchell et al., 1981, Proc. Natl Acad. Sci. USA 78: 3165-3169; Cruise et al., 1981, Acta Tropica 38: 437-447) and capable of detecting the presence of 1 worm (Garcia et al., 1983, loc. cit.), was used to prove that the parasite-negative 129/J mice did not have cryptic infections. Using a lung petechiae assay (Olivier, 1952, Am. J. Hyg. 29: 832-841) at various days PI, evidence was obtained that some worms remained established beyond the lung schistosomule stage and that worm attrition occurred at some time between 1 and 3 wk of infection. Thus the 129/J mouse/S. japonicum model may provide a means to analyze late phase attrition in a primary infection in what is regarded as a permissive host species. Totally unknown is the reason for variability within the supposedly inbred 129/J mouse strain. The contributions of nonimmunological factors demonstrated in the S. mansoni/rat modl also remain unknown (Knopf, 1982, Vet. Parasit. 10: 249-254; Phillips and Colley, 1978, Progr. Immunol. 24: 49-182). Sera from 129/J mice, repeatedly exposed to cercariae, were produced in order to examine any exaggerated antibody responses in resistant 129/J mice directed against labeled, extracted antigens of adult worms using immunoprecipitation, gel electrophoresis and autoradiography. It was first necessary to establish that a proportion of repeatedly-exposed 129/J mice was still resistant to infection. Data presented in Figure 1 establish that this is so and confirm previous data. Thus, 90% of BALB/c mice had worm numbers > 10 per mouse (determined by portal perfusion and liver dissection) after percutaneous challenge with 25 cercariae from field-collected snails (Mindoro, Philippines). The majority of C3H/He mice also had high worm burdens. In contrast, 2 distinct groups of 129/J mice were apparent-those with low numbers of worms and those with high numbers, the latter group accounting for 36% of the mice. In 129/J mice