An in vitro model of granuloma formation was used to study the cellular immune responses of Schistosoma mansoni-infected patients. The purposes of this study were to determine the relationship of granulomatous hypersensitivity to S. mansoni eggs in recent, well-defined infections and long-term chronic infections, and to determine the role of T cell subsets (OKT3, 4, and 8) defined by monoclonal antibodies in granulomatous hypersensitivity. Peripheral blood mononuclear cells obtained from patients with recent S. mansoni infections demonstrated increased granulomatous hypersensitivity responses in vitro when compared to peripheral blood mononuclear cells obtained from patients infected for 5 yr or more. The selective removal of infected for 5 yr or more. The selective removal of OKT3+ or OKT4+ cells reduced the ability of peripheral blood mononuclear cells to form granulomas in vitro. Positive selection for OKT4+ T cells produced optimal granulomatous hypersensitivity when compared to that produced by the unfractionated peripheral blood mononuclear cell population. OKT8+ cells demonstrated no ability to form granulomas in vitro. Selective removal of OKT8+ T cells produced variable results in the ability of the remaining peripheral blood mononuclear cells to form granulomas in vitro. These studies demonstrate the feasibility of investigating granulomatous hypersensitivity and immunoregulatory mechanisms operative in S. mansoni-infected patients by using in vitro technology.
telangiectasia, fatigue and headache. One patient experienced Grade 5 neutropenic sepsis considered unrelated to TRC105 or B. Analysis of the angiogenic biomarkers will be presented. Conclusion: Induction treatment for six 3-week cycles withTRC105 + B, P, and C, followed by maintenance therapy with TRC105 + B until disease progression was tolerable and did not potentiate the toxicity of B, P or C. The combination of TRC105 + B, P and C demonstrated signs of activity including PR in 4 of 12 evaluable pts.
To understand factors that modulate the amount and removal of antigen found in the circulation of schistosome-infected mice, a specific schistosome antigen, GASP, found in the circulation of infected animals, was radiolabeled with Bolton-Hunter reagent and injected into infected and control mice. The rates of clearance, levels of antigen binding, and the fate of the injected antigen were determined. Within 1 to 3 wk after injection, infected animals developed enhanced antigen clearance that paralleled the increase in antibody to GASP. Lightly infected animals showed faster clearance rates and increased antibody levels compared with heavily infected mice. The level of antibody in the sera, irrespective of the duration or intensity of infection, correlated with enhanced clearance. Heavily infected animals removed preformed immune complexes as rapidly as lightly infected mice. This indicates that the relative inability to clear antigen was not due to blockade of Kupffer cells. Circulating GASP antigen, determined by countercurrent electrophoresis, was detected in heavily infected animals in the presence of increased antibody, suggesting that circulating GASP was in immune complexes. Both free and complexed antigen were primarily cleared by the liver and then excreted in the urine as low m.w. nonantigenic products. With sensitive radioimmunoassays, GASP could not be detected in infected human or mouse urine.
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