This proposal describes the continuation of studies to investigate basic immunologic and immunopathologic mechanisms in experimental murine schistosomiasis mansoni. They involve the identification of the major stimulatory egg antigens responsible for eliciting T cell-mediated granulomatous hypersensitivity and immunopathologic damage, as well as the elucidation of the basic mechanisms that underlie the phenomenon of immunological down-regulation (immunomodulation), characteristic of this disease. T cell clones will be produced to analyze the basis of the cell-mediated antischistosomal immune response. Clone phenotypes will be established. Clonality will be verified by Southern blot analysis. Fine specificities recognized by the clones will be ascertained by stimulation with, individual antigenic egg components following fractionation by agarose-isoelectric focusing and high pressure liquid chromatography, and/or identification by monoclonal antibody analysis. The genetic restrictions of the response will be determined. Functional capabilities of SEA-specific T cell clones will be ascertained in vivo. The hypothesis that granuloma macrophages induce a state of unresponsiveness to antigen in specific T cell clones will be tested. This may offer a novel explanation for the phenomenon of immunomodulation, which has, so far, defied satisfactory understanding. This hypothesis will also be implemented by assessing the effect of specific T cell clone unresponsiveness-inducing regimens on the development and course of a challenge schistosomal infection in vivo. These experiments will contribute to the understanding of the basic immunological mechanisms in schistosomiasis, and are expected to have a direct impact in the development of preventive and therapeutic approaches against the pathology resulting from this disease.
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