Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.

The granulomatous inflammatory response induced by schistosome eggs entrapped in the microvasculature of host tissues is considered responsible for much of the symptomatology of schistosomiasis. However, the evolutionary role of the egg granuloma in the host-parasite relationship is not yet well defined. Some evidence indicates that the lesion may protect the host, either by shielding tissues against toxic egg products, or by interfering with the migration patterns of secondary infections, and thereby non-specifically contributing to the host's acquired "immunity". We here review earlier work concerned with the role of the egg granuloma in the host-parasite relationship in schistosomiasis, and we present new experimental evidence to suggest that the function of this cell-mediated immune response might, in addition to its putative host protective function, facilitate the extravasation of parasite eggs in the mesenteries, and thereby contribute directly to the continuation of the schistosome life-cycle.

CBA mice which had been deprived of their T cells by a combination of adult thymectomy and injection of rabbit anti-mouse thymocyte serum failed to excrete as many Schisrosoma mansoni eggs in their faeces as immunologically intact controls. This failure of parasite egg excretion was not obviously attributable to any marked change in the amount of faecal matter produced, or to a change in the size of the worm burden, or to the number or distribution ofeggs in the tissues as a result of T-cell deprivation. S. munsoni eggs freshly isolated from T-cell-deprived mice and injected intravenously into normal animals, induced lung granulomas which were the same size as those induced by injection of eggs from normal donors. The rate of S. mansoni egg excretion was not affected by the density of eggs in the tissues, in as much as there was a linear relationship between the number of tissue-bound eggs and the number of eggs detected in the faeces. Treatment of infected mice with the immunosuppressant hydrocortisone acetate also induced a marked reduction in the rate of egg excretion. Injections of serum derived from chronically infected normal mouse donors increased the rate of egg excretion in both T-cell-deprived and steroid-treated mice, but the degree of reconstitution obtained by daily serum injections was only partial relative to normal egg excretion rates. Treatment of infected normal or deprived serumtreated mice with cobra venom factor to reduce serum complement C3 levels had no effect on the rate of S. mansoni egg excretion.Recent studies on Schistosoma mansoni-infected mice have demonstrated a marked Present addresses:

The effects of various immunosuppressive regimes on the survival and liver pathology of mice infected with Schistosoma mansoni were investigated. T-cell deprivation before infection (by adult thymectomy and subsequent anti-thymocyte serum administration), or treatment with hydrocortisone or cyclophosphamide or azathioprine after infection, all reduced survival of infected mice when compared with immunologically intact, infected mice. T-cell deprivation or steroids produced severe liver damage in infected mice despite a reduction in the size of the peri-oval granulomatous inflammatory reaction. Administration of chronic infection serum reduced liver damage in both T-cell-deprived and steroid-treated animals, but improved survival only in the deprived animals and not to the level seen in normal infected mice. The liver damage in immunosuppressed mice was not due to opportunistic bacterial infection. Thus, although immunosuppression reduced the granulomatous response to schistosome eggs in the livers of infected mice (as it does to eggs injected intravenously into the lungs), survival time was decreased. The relevance of these findings to human S. mansoni infections is discussed.

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