IMMUNOLOGIC STUDIES ON SCHISTOSOMIASIS

血吸虫病的免疫学研究

• 批准号: 2566727
• 负责人: A SHER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2566727
• 关键词: Schistosoma; active immunization; egg /ovum; gene targeting; granuloma; helminthic antigen; human tissue; humoral immunity; immunology; immunoregulation; immunotherapy; interferon gamma; interleukin 10; interleukin 12; laboratory mouse; life cycle; nonhuman therapy evaluation; schistosomiasis; spleen; vaccines

The aim of this research program is to investigate mechanisms of protective immunity and immunopathology in schistosomiasis with the ultimate goal of immunologic intervention. Progress was achieved in the following areas during the year. A. Demonstration of IL-12-stimulated humoral immunity against schistosome infection. Interleukin-12, when coadministered repeatedly with an irradiated cercarial vaccine, was shown to boost protective humoral responses resulting in nearly complete resistance to challenge infection. B. Analysis of egg granuloma formation and downmodulation in knockout mice. Mice genetically deficient in IFN-gamma, IL-10 or CD8+ T cells were shown to undergo normal granuloma formation upon acute infection with S. mnsoni as well as downmodulate egg granuloma size during the chronic phase. In contrast, B cell (mu MT) knockout mice developed enlarged acute granulomas which failed to modulate in late infection. These studies thus reveal a major immunoregulatory function of B lymphocytes on schistosome egg pathology. C. Cross-regulatory cytokine function in spleen cells from hepatosplenic patients. Spleen cells from surgically splenectomized hepatosplenic patients showed in vitro cytokine responses comparable to peripheral blood mononuclear cells of the same individuals. Endogenous IL-10 was shown to be a potent downregulator of IFN-gamma and IL-12 Ag specific responses in these patients while exogenous IL-12 in some individuals restored suppressed IFN-gamma and IL-12 responses while stimulating IL-10 production.

该研究项目的目的是研究 血吸虫病的保护性免疫和免疫病理 免疫干预的最终目标。 取得了进展 在这一年中，以下地区。 A. 证实IL-12刺激的抗人免疫球蛋白的体液免疫 可怕的感染。 白细胞介素-12，当重复联合给药时 与辐射尾蚴疫苗，被证明可以提高保护性 体液反应导致对挑战几乎完全抵抗 感染 B。 基因敲除中虫卵肉芽肿形成和下调的分析 小鼠 IFN-γ、IL-10或CD 8 + T细胞遗传缺陷的小鼠 在急性感染时， 链球菌以及下调虫卵肉芽肿的大小， 慢性期 相反，B细胞（μ MT）敲除小鼠 扩大的急性肉芽肿，在晚期感染中未能调节。 因此，这些研究揭示了B的主要免疫调节功能 淋巴细胞对受精卵病理学的影响。 C. 肝脾脾细胞交叉调节细胞因子功能的研究 患者 手术切除脾脏的肝脾细胞 患者表现出与外周血相当的体外细胞因子反应 同一个体的血液单核细胞。 内源性IL-10是 显示为IFN-γ和IL-12 Ag特异性的有效下调剂 在这些患者中，外源性IL-12在某些个体中 恢复了抑制的IFN-γ和IL-12应答，同时刺激IL-10 生产