This research project comprises the cellular/molecular analysis of the immunoregulatory, inflammatory and fibrotic mechanisms active in granulomatous schistosomiasis mansoni. Our objective is to elucidate the granulomatous process and design immunologic interventions to ameliorate granulomatous pathology. The research objectives are divided into 4 interrelatled areas: 1. Induction of T suppressor (TS) cells with isolated schistosome egg antigen, idiotype-antiidiotype (id--anti id) interactions in granuloma modulations. Ts cell inducer antigen is isolated with monoclonal antibodies and immunoaffinity. Induction of afferent, efferent TS cells is verified in vivo, in vitro. Id-anti id interactions in T cell functions, granulomal modulation are examined. Premature modulation of schistosomiasis is sought by immunologic means. 2. Functional studies on granuloma T lymphocytes, the role of interleukin 2 (IL-2) in the granulomatous process. Mode of inflammatory (TDH) and TS lymphocyte interaction is analyzed in the vigorous, modulated granulomas. The significance of IL-2 receptor display IL-2, inflammatory lymphokine production in granuloma formation is evaluated, the regulatory role of granuloma TS cells and id-anti id interactions in lyumphokine production and granuloma modulation is confirmed. 3. Fractionation, pyhenotypic, functional characterization of liver, intestinal granuloma macrophages, monocyte supply-macrophage turnover. Macrophages isolated from enzymatically dispersed granulomas are fractionated by density gradient centrifugation. Each fraction is examined for maturation markers by immunofluorescence, phagocytic, secretory and accessory/regulatory functions. Role of colony stimulating factor in monocyte supply and granuloma macrophage turnover is elucidated. 4. Collagen isotype synthesis and resorption in granulomas, functional studies on the granuloma fibroblast, isolation of fibrogenic factor from egg antigens. Granuloma collagen isotype synthesis and resorption is delineated in untreated and drug cured mice biochemically and with collagen specific cDNA probes. Proliferation and collagen synthesis are compared in fibroblasts of the vigorous and modulated granulomas. Neutral protease-protease inhibitors in resorption are assessed. Isolated egg antigen is examined for fibroblast enhancing/cytopathic effect.
