In schistosomiasis japonica the basic pathologic lesion is the granulomatous inflammation that occurs around eggs trapped in host tissues. This occurs primarily in the liver and results in periportal inflammation, fibrosis, obstruction of portal blood flow, portal hypertension and clinically, bleeding esophageal varices. During the transition from acute to chronic infection there is an immunologic down regulation, termed modulation which results in less granulomatous inflammation, and lower portal pressures. The long term objective of this proposal is to dissect the mechanisms of this beneficial immunologic adjustment and its associated amelioration of clinical disease.
The specific aims are: 1. To characterize humoral mechanism(s) of modulation in vitro. The possible role of anti-egg antibody, immune complexes and/or anti-idiotypic antibody will be examined. Immunoregulatory immunoglobulin will then be cloned by the fusion of splenocytes from infected mice with a B cell myeloma. 2. Characterize in vitro immunoregulatory T cells using T cell clones, T cell hybrids and their immunomodulatory products from S. japonicum infected mice. 3. To examine the effect of mediators from cloned cells on in vivo modulation. This section will utilize the adoptive transfer of monoclonal antibody, cloned T cells, and T cell products into acutely infected recipient mice. Effects on the morbidity, granuloma size, portal pressure and hepatic fibrosis as well as delayed and immediate footpad hypersensitivity to egg antigen will be determined.
