Experimental murine models of schistosomiasis mansoni have characterized the delayed type hypersensitivity cellular responses to eggs lodged in the tissues of the host. The cell types involved in the early acute granulomatous responses are lymphocytes (T cells, B cells and plasma cells), macrophages (monocytes, epitheloid cells and giant cells) fibroblasts, granulocytes (eosinophils, neutrophils), and mast cells (1-6). Furthermore, studies of granulomatous hypersensitivity in murine schistosomiasis have demonstrated a role for lymphocyte subsets in granuloma formation (7, 8). Previously published studies using an in vitro granuloma model established a role for T cell subsets in granuloma formation and identified a suppressor T cell pathway in granuloma modulation (9, 10). This proposal outlines in vitro technology which will enable the investigator to analyze granulomatous hypersensitivity without risk to the patient from invasive surgical procedures. A thorough understanding of chronic granulomatous disease in schistosomiasIs and the immunologic factors that contribute to or ameliorate morbidity will provide sound rationale for the development of either prophylactic protocols or clinical treatments that might reduce or ameliorate morbidity. Other investigators have identified immunoregulatory mechanisms operative in human schistosomiasis. These mechanisms were defined using antigen or mitogen induced proliferation of peripheral blood mononuclear cells and include serum factors, adherent mononuclear cells and suppressor T cells (11-20). This proposal intends to examine granuloma formation and modulation in human schistosomiasis, using an in vitro bead granuloma model which recapitulates the process of delayed type hypersensitivity granulomas, and to provide new knowledge of cell-cell interactions which result in the development of chronic granulomatous disease. The objectives of this proposal are to determine the role of human T cell subsets on granuloma formation and modulation, and to characterize the function of the T cell subsets as to inducer, effector or suppressor, and to correlate the immunoregulatory circuits with the degree of clinical morbidity.
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|Parra, J C; Doughty, B; Colley, D G et al. (1992) Human schistosomiasis mansoni: studies on in vitro granuloma modulation. Mem Inst Oswaldo Cruz 87 Suppl 5:79-81|
|Parra, J C; Gazzinelli, G; Goes, A M et al. (1991) Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. II. In vitro granuloma modulation induced by polyclonal idiotypic antibodies. J Immunol 147:3949-54|
|Goes, A M; Gazzinelli, G; Rocha, R et al. (1991) Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Am J Trop Med Hyg 44:434-43|
|Goes, A M; Rocha, R S; Gazzinelli, G et al. (1989) Production and characterization of human monoclonal antibodies against Schistosoma mansoni. Parasite Immunol 11:695-711|
|Doughty, B L; Goes, A M; Parra, J C et al. (1987) Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. I. Granuloma formation and modulation around polyacrylamide antigen-conjugated beads. Mem Inst Oswaldo Cruz 82 Suppl 4:47-54|