Basic Research on Protective Immunity against Experimental Hemoprotozoan Infections

实验性血液原虫感染的保护性免疫基础研究

• 批准号: 03660318
• 负责人: IGARASHI Ikuo
• 金额: $ 1.47万
• 依托单位: The Research Center for Protozoan Molecular Immunology, Obihiro University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03660318/
• 关键词: Murine Babesia; Protective immunity; CD4^+ T cells; Gamma interferon; Cross-reactive antigen; Renal pathology; Immunopathology; Nonspecific immunity; バベシア原虫; 感染防御; CD_4陽性細胞; ガンア-インターフェロン; 赤血球内寄生原虫; 感染防抑; CD4^+細胞; 感染防御免疫

Role of cell-mediated immunity in Babesia infection was investigated using mouse models in the present study. In lethal Babesia rodhaini infection, drug-cured mice showed 75% protection against challenge infection with B.rodhaini and a humoral immunity appears to be major role in the effector phase of immunity. Mice which were cured first infection with anti-Babesia durg and survived with challenge infection, showed 100% protection against B.radhaini infection, Lyt1^+ and Lyt2^+ T cells may contribute in controlling secondary infection.In B.microti infection, while mice sufferd high parasitemia, but recovered naturally from their primary infection, nu/nu mice and SCID had a higher peak parasitemia and failed to clear the infection. These results demonstrated that T lymphocytes are necessary for the resolution of B.microti infection. Mice depleted of CD4^+ T cells with monoclonal antibody (mAb) had high parasitemia and failed to control the infection, while depletion of CD8^+ cells had … More no effect on the course of infection. Culture supernatants of spleen cells from control and CD8^+ cells depleted, but not from CD4^+ depleted mice, showed high concentration of IFN-gamma. Treatment of infected mice with anti-IFN-gamma mAb showed higher parasitemia than that of the control group. These results suggest that IFN-gamma produce by CD4^+ T cells, at least in part, is responsible for the control of acute infection with B.microti in mice.Mab, recognizing 70,30 kDa antigens of B.microti and challenged with B.rodhaini, was produced from mice infected with B.microti and challenged with B.rodhaini. Administration of the mAb gave the delay of onset of parasitemias in mice. Mice which were exposed to oocysts of Isospora felis, showed absolute resistance against B.microti infection on 28th day post-exposure of oocysts. CD4^+ T cells induced by I.felis infection provides mice protection against B.microti.Pathological changes were examined in the kidneys and liver of mice of two babesioses. Severe damages to kidneys and liver were observed in B.rodhaini infection rather than in B.microti infection. Electron-dense deposits were demonstrated in the mesangial matrix and along the glomerular basement membrane and these deposits were suggested as immune complexes by immunohistochemistry. Less

在本研究中使用小鼠模型研究了细胞介导的免疫在巴贝虫感染中的作用。在致命的罗氏巴贝虫感染中，药物治愈的小鼠对罗氏巴贝虫的攻击感染具有 75% 的保护作用，体液免疫似乎在免疫效应阶段发挥着主要作用。用抗巴贝虫药物治愈首次感染并在攻击感染后存活的小鼠，对 B.radhaini 感染表现出 100% 的保护，Lyt1^+ 和 Lyt2^+ T 细胞可能有助于控制继发感染。在 B.microti 感染中，虽然小鼠遭受高寄生虫血症，但从初次感染中自然恢复，nu/nu 小鼠和 SCID 小鼠具有更高的寄生虫血症峰值，并且 未能清除感染。这些结果表明，T 淋巴细胞对于消除田鼠芽孢杆菌感染是必需的。用单克隆抗体 (mAb) 去除 CD4^+ T 细胞的小鼠寄生虫血症较高，无法控制感染，而去除 CD8^+ 细胞对感染过程没有影响。来自对照和 CD8^+ 细胞耗尽的小鼠（而非 CD4^+ 耗尽的小鼠）的脾细胞的培养上清液显示出高浓度的 IFN-γ。用抗-IFN-γ单克隆抗体治疗受感染的小鼠显示出比对照组更高的寄生虫血症。这些结果表明，CD4^+ T 细胞产生的 IFN-gamma 至少部分负责控制小鼠中的 B.microti 急性感染。Mab 识别 70,30 kDa 的 B.microti 抗原并用 B.rodhaini 攻击，由感染 B.microti 并用 B.rodhaini 攻击的小鼠产生。施用单克隆抗体可以延迟小鼠体内寄生虫血症的发生。接触猫等孢子虫卵囊的小鼠在接触卵囊后第28天表现出对田鼠小孢子虫感染的绝对抵抗力。猫巴贝虫感染诱导的 CD4+ T 细胞为小鼠提供了针对田鼠巴贝斯虫的保护。对两种巴贝虫病小鼠的肾脏和肝脏进行了病理学变化的检查。在罗氏疏螺旋体感染中观察到对肾脏和肝脏的严重损害，而不是在田鼠疏螺旋体感染中。在系膜基质和沿着肾小球基底膜中显示出电子致密沉积物，并且通过免疫组织化学，这些沉积物被认为是免疫复合物。较少的

项目成果

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Shimada, T., Igarashi, I., Maki, Y., Claveria, F.G., Saito, A.and Suzuki, N.: "Cellular subsets involved in protective immunity to Babesia rodhaini infection in BLAB/c mice." J.Protozool.Res.1. 35-44 (1991)

Shimada, T.、Igarashi, I.、Maki, Y.、Claveria, F.G.、Saito, A. 和 Suzuki, N.：“参与 BLAB/c 小鼠对巴贝虫感染的保护性免疫的细胞亚群。”

Igarashi, I., Hosomi, T., Kaidoh, T., Omata, Y., Saito, A.Suzuki, N.and Aikawa, M.: "Comparison of damage to kidneys and liver caused by lethal Babesia rodhaini infection and non-lethal Babesia microti infection in mice." J.Protozool.Res.3. 144-155 (1993)

Igarashi, I.、Hosomi, T.、Kaidoh, T.、Omata, Y.、Saito, A.Suzuki, N. 和 Aikawa, M.：“致死性巴贝虫罗德海尼感染和非致命性巴贝虫感染对肾脏和肝脏造成的损害的比较

Inoue, N., Omata, Y., Igarashi, I., Saito, A., Claveria, F.G.and Suzuki, N.: "Babesia rodhaini and Babesia microti : Cross-Immunity and Cross-Antigens." J.Protozool.Res.4. 98-104 (1994)

Inoue, N.、Omata, Y.、Igarashi, I.、Saito, A.、Claveria, F.G. 和 Suzuki, N.：“罗德海尼巴贝虫和田鼠巴贝虫：交叉免疫和交叉抗原。”

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A.Saito：“活性氧中间体清除剂对活化巨噬细胞抗弓形虫活性的影响”寄生虫学研究。