To determine the in vivo role of IL‐12 in the development of protective immunity in visceral leishmaniasis caused by Leishmania donovani, we examined the course of L. donovani infection in IL‐12‐deficient C57BL / 6 (IL‐12– / –) mice. IL‐12– / – mice displayed significantly higher parasite burdens in their livers and spleens than wild‐type C57BL / 6 mice throughout the course of infection. Despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in L. donovani‐infected IL‐12– / –. Moreover, livers and spleens from IL‐12– / – mice displayed significantly less inflammation and poorly formed granulomatous lesions than those from IL‐12+ / + mice throughout the course of infection. Antigen‐stimulated splenocytes from IL‐12– / – mice produced significantly less IFN‐γ but more IL‐4 than IL‐12+ / + mice. These findings indicate that although endogenous IL‐12 is critical for the development of protective immunity to L. donovani, it is also responsible for inducing the significant immunopathology associated with visceral leishmaniasis.

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To investigate the role of antibody in the pathogenesis of hepatic granulomas around schistosome eggs, mice were depleted of B cells by treatment from birth with anti-IgM serum and were subsequently infected with Schistosoma japonicum or S. mansoni. Anti-IgM treatment did not affect the development or fecundity of the worms or the larvae within the egg shells. Normal circumoval granulomas were present in the livers of B cell depleted mice 7 or 8 weeks after infection clearly indicating that antibody and immune complexes have no necessary role in the formation of granulomas. Hepatic fibrosis was also similar in B cell depleted and untreated mice at these times. Ten weeks after infection the size of S. japonicum egg granulomas in untreated mice had decreased but no change in the size of granulomas had occurred in B cell depleted mice, and hepatic fibrosis was more marked in treated than in untreated mice. Similar changes were noted in S. mansoni infected mice, assayed at 8 and at 12-13.5 weeks after infection. The effects of B cell depletion in the more chronic infections may be related to the absence of antibody but could also be caused by an influence on B cell-dependent suppressor T cells.