A study on involvement of cytokines in immune response to parasite infections using immune response-reacted gene defective mice

使用免疫反应反应基因缺陷小鼠研究细胞因子参与寄生虫感染免疫反应

• 批准号: 07457066
• 负责人: SENDO Fujiro
• 金额: $ 4.1万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457066/
• 关键词: IFN-gamma recetor gene knockout mouse; IL-4 knockout mouse; cytokine; Leishmania major; enzyme-linked immunospot assay; 免疫関連遺伝子欠損マウス; IL-4; IFN-_Y

Cytokines play a variety of crucial regulatory roles in the host response to parasites. To analyze complecated immune responses in parasite infections, we investigated effects of IFN-gamma and IL-4 on parasite infections by using IFN-gamma receptor and IL-4 gene knockout mice (IFN-gamma R^% and IL-4^%, respectively), wild type C57BL/6 mice, resistant to L.major, and wild type BALB/c micc, suceptible to this organism. The obtained results are as follows. 1.IL-4^% and C57BL/6 mice showed a weak footpad swelling, when these mice were infected s.c.with L.major. On the other hand, high intensity of footpad swelling was observed in IFN-gamma R^% and BALB/c mice infected with L.major. 2.The number of IFN-gamma or IL-4 producing cells were measured in the popliteal lymphnodes, the spleen, and the liver of BALB/c and C57BL/6 mice using enzyme-linked immunospot assay and flow cytometry. The reaction as follows. (1) IFN-gamma Producing cells were detected in the presence of L.major antigens in BALB/c and C57BL/6 mice, and the number of the IFN-gamma Producing cells in C57BL/6 mice was more than that in BALB/c mice. (2) The IFN-gamma producing cells could not be detected in vitro in the abscence of the antigens in both mice by 5 weeks post infection. (3) IL-4 producing cells were detected from the spleen and the liver of BALB/c mice and increased with the progress of the infection. (4) Phenotype of IL-4 producing cells in the liver of BALB/c mice were gammadelta^+T cells, alphabeta^+T cells, and CD4^-CD8^- cells. gammadelta^+T cells incrcased at 2 week post infection and alphabeta^+T cells incrcased at 4 week. CD4^-CD8^- cells produced IL-4 during only early phase of the infection. Studies to analyze these phenomena are currently underway.

细胞因子在宿主对寄生虫的反应中起着多种重要的调节作用。为了分析寄生虫感染中的复杂免疫应答，我们通过使用IFN-γ受体和IL-4基因敲除小鼠（分别为IFN-γ R^%和IL-4^%）、抗硕大利什曼原虫的野生型C57 BL/6小鼠和对该生物体易感的野生型BALB/c小鼠来研究IFN-γ和IL-4对寄生虫感染的影响。所得结果如下。1.IL-4/1%和C57 BL/6小鼠皮下感染L. major后，表现出较弱的足垫肿胀。另一方面，在IFN-γ R %和感染了硕大乳杆菌的BALB/c小鼠中观察到高强度的足垫肿胀。2.采用酶联免疫斑点法和流式细胞术检测BALB/c和C57 BL/6小鼠腘淋巴结、脾脏和肝脏中IFN-γ或IL-4产生细胞的数量。反应如下。(1)在BALB/c和C57 BL/6小鼠体内，在存在L.major抗原的情况下，可检测到IFN-γ产生细胞，且C57 BL/6小鼠体内IFN-γ产生细胞的数量多于BALB/c小鼠。(2)到感染后5周，在两种小鼠中的抗原结合中不能在体外检测到IFN-γ产生细胞。(3)在BALB/c小鼠的脾脏和肝脏中检测到IL-4产生细胞，并随着感染的进展而增加。(4)BALB/c小鼠肝脏中IL-4产生细胞的表型为γ δ ^+T细胞、α ^+T细胞和CD 4 ^-CD 8 ^-细胞。γ δ ^+T细胞在感染后2周增加，α ^+T细胞在感染后4周增加。CD 4 ^-CD 8 ^-细胞仅在感染早期产生IL-4。目前正在对这些现象进行分析研究。