Molecular immunological study on the susceptibility and morbidity of T cell-chimeric mice to Angiostrongylus cantonensis

T细胞嵌合小鼠对广州管圆线虫的易感性和发病性的分子免疫学研究

基本信息

批准号：
10470065
负责人：
YOSHIMURA Kentaro
金额：
$ 6.98万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

The results obtained are as follows : 1. A study using B10 congenic mice indicated that murine morbidity and susceptibility to Angiostrongylus cantonensis infection are not linked to the H-2 complex but rather to non-H-2 background genes and also that there is no significant relationship between antigen-specific antibody responses and murine susceptibility or morbidity to A.cantonensis infection. 2. A study using INF-γ knockout mice suggested that INF-γ itself did not affect the outcome of A.cantonensis infection in mice. 3. C.B-17 strain mice have the defective eosinopoiesis and are thereby incapable of killing intracranial worms of A.cantonensis. This is probably due to the impaired expression of β-chain mRNA in bone marrow cells of C.B-17 strain. 4. A study using bone marrow chimeric mice between C.B-17 and C57BL/6 mice suggests that the bone marrow derived cells are primarily involved in the expression of morbidity in A.cantonensis infected C.B-17 mice but non-bone marrow derived c … More ell types are also concerned partly. 5. T cell-chimeric mice were produced by the procedure that BALB/c-nu/nu mice which had been irradiated with sublethal dose of X ray and additionally treated with anti-Thy-1.2 antibody were reconstituted with homologous bone marrow cells and then transferred with thymus cells derived from C57BL/6 or BALB/c. A majority of BALB/c-T cell-chimeric mice died before A.cantonensis infection and the infected BALB/c-T cell-chimeric mice also died soon after infection. Sham chimeric mice showed the impaired worm development when compared with nu/nu mice, and also exhibited marked body weight loss and high mortality after A.cantonensis infection although they yielded a similar level of worm burdens as nu/nu or +/+ mice. These data suggest that T cells of BALB/c are associated with morbidity after infection whereas T cells from C57BL/6 contribute to improving morbidity. 6. F1, F2 and back-cross progenies between C.B-17 and C57BL/6 mice were examined for susceptibility, eosinophil responses and morbidity. These responses were found to be controlled by multiple genes, and a weak positive correlation was recognized between worm recovery and the level of eosinophils in cerebrospinal fluid. 7. Splenic CD4^+T cells from infected BALB/c mice showed a proliferative response against several protein antigens ranging from 22 to 56 kD.This suggests that these responses by CD4^+T cells are responsible for inducing morbidity. Less

所获得的结果如下：1。使用B10过敏小鼠的研究表明，鼠的发病率和对植物造成的鼠标感染的敏感性与H-2复合物无关，而与非H-2背景基因相关，并且与非H-2背景基因相关，并且抗原特异性抗体反应和鼠类易感性或杂经对A. CANTONENSIS的抗原特异性抗体反应之间没有显着的关系。 2。一项使用INF-γ基因敲除小鼠的研究表明，INF-γ本身并不影响小鼠腹膜内感染的结果。 3。C.B-17菌株小鼠的嗜酸性嗜酸菌病缺乏，因此无法杀死腹膜内脑内蠕虫。这可能是由于C.B-17菌株的骨髓细胞中β链mRNA的表达受损。 4。在C.B-17和C57BL/6小鼠之间使用骨髓嵌合小鼠的一项研究表明，骨髓衍生的细胞主要参与A. cantonensis感染的C.B-17小鼠的发病率，但非骨骨髓衍生的C ...更多的ELL类型也部分涉及。 5。T细胞示聚小鼠是通过用X射线辐照的BALB/C-NU/NU小鼠进行的，并用抗Thy-1.2抗体对抗thy-1.2抗体进行了处理，并用同源骨髓细胞重构，然后用C57Bl/6或6或6或6或6或6或6或C57bl/6或6或C57bl/6或C57bl/c。大多数BALB/C-T细胞 - 晶状体小鼠在腹膜内感染之前就死亡，感染的BALB/C-T细胞旋转小鼠也在感染后不久就死亡。与NU/NU小鼠相比，假嵌合小鼠表现出受损的蠕虫发育，并且在a.cantonensis感染后暴露了明显的体重减轻和高死亡率，尽管它们产生了与Nu/Nu或 +/ +/ +小鼠相似的蠕虫伯氏。这些数据表明，BALB/C的T细胞与感染后的发病率有关，而C57BL/6的T细胞有助于提高发病率。 6。F1，F2和C.B-17和C57BL/6小鼠之间的后代有易感性，嗜酸性粒细胞反应和发病率。这些反应被发现由多个基因控制，并且在脑脊液中蠕虫恢复与嗜酸性粒细胞水平之间识别出弱的正相关。 7。来自感染的BALB/C小鼠的脾脏CD4^+T细胞显示出对几种在22至56 kD之间的蛋白质抗原的增生剂反应。这表明CD4^+T细胞对这些反应造成了诱导的发病率。较少的