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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470065/
• 关键词: Angiostrongylus cantonensis; chimeric mice; C57BL; 6; BALB; c; C.B-17; IFN-γ knockout mouse; B10 congenic mice; Genetics; 好酸球; T細胞キメラ; T cell blot; 抗IL-4モノクローナル抗体; 骨髄キメラマウス; T細胞キメラマウス; 好酸球増多; 病態; X線照射; Angiostrongylus cantonensis; H-2

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

主要研究结果如下：1.一项使用B10同源小鼠的研究表明，小鼠对广州管圆线虫感染的发病率和易感性与H-2复合体无关，而是与非H-2背景基因有关，并且抗原特异性抗体应答与小鼠对广州管圆线虫感染的易感性或发病率之间没有显著关系。2.一项使用INF-γ基因敲除小鼠的研究表明，INF-γ本身并不影响小鼠中广州管圆线虫感染的结果。3. C.B-17品系小鼠具有有缺陷的嗜酸性粒细胞生成，因此不能杀死广州管圆线虫的颅内蠕虫。这可能与C.B-17株骨髓细胞β链mRNA表达受损有关。4.一项使用C.B-17和C57 BL/6小鼠之间的骨髓嵌合小鼠的研究表明，骨髓来源的细胞主要参与了广州管圆线虫感染的C.B-17小鼠的发病率表达，而非骨髓来源的细胞主要参与了C. ...更多信息 也部分涉及到细胞类型。5.将经亚致死剂量X射线照射并额外用抗Thy-1.2抗体处理的BALB/c-nu/nu小鼠用同源骨髓细胞重建，然后用来自C57 BL/6或BALB/c的胸腺细胞转移，制备T细胞嵌合小鼠。大多数BALB/c-T细胞嵌合小鼠在感染广州管圆线虫前死亡，感染的BALB/c-T细胞嵌合小鼠也在感染后不久死亡。与nu/nu小鼠相比，假嵌合小鼠显示出蠕虫发育受损，并且在广州管圆线虫感染后也表现出显著的体重减轻和高死亡率，尽管它们产生与nu/nu或+/+小鼠相似的蠕虫负荷水平。这些数据表明，BALB/c的T细胞与感染后的发病率相关，而来自C57 BL/6的T细胞有助于改善发病率。6.检查了C.B-17和C57 BL/6小鼠之间的F1、F2和回交后代的易感性、嗜酸性粒细胞反应和发病率。这些反应被发现是由多个基因控制，并确认之间的弱正相关性蠕虫恢复和脑脊液中的嗜酸性粒细胞的水平。7.感染BALB/c小鼠的脾脏CD 4 ^+T细胞对22 ~ 56 kD的几种蛋白质抗原表现出增殖反应，这表明CD 4 ^+T细胞的这些反应是导致发病的原因。少

项目成果

吉村堅太郎: "小児の感染症(II)広東住血線虫症."小児科臨床. 52. 625-627 (1999)

吉村健太郎：“儿童传染病（II）广东血吸虫病。” 52. 625-627 (1999)

Yoshimura K, Sugaya H, Aoki M, Ishida K: "SCID mice show a similar susceptibility to Angiostrongylus cantonensis as do wild-type mice of the C.B-17 strain."Parasitol Res. 86. 542-550 (2000)

Yoshimura K、Sugaya H、Aoki M、Ishida K：“SCID 小鼠对广州管圆线虫表现出与 C.B-17 品系野生型小鼠相似的易感性。”Parasitol Res。

Koyama T,Abe T,Sugaya H,Koizumi A,Yoshimura K: "IL-3-dependent murine bone marrow derived mast cells express Fas but are resistant to Fas-mediated apoptosis."Akita J Med. 25. 231-237 (1998)

Koyama T、Abe T、Sugaya H、Koizumi A、Yoshimura K：“IL-3 依赖性小鼠骨髓来源的肥大细胞表达 Fas，但对 Fas 介导的细胞凋亡具有抵抗力。”Akita J Med。

吉村堅太郎: "寄生虫疾患における好酸球の役割"細胞. 30. 321-325 (1998)

Kentaro Yoshimura：“嗜酸性粒细胞在寄生虫病中的作用”细胞。30. 321-325 (1998)

吉村 堅太郎: "日本における寄生虫学の研究 第6巻"財団法人 目黒寄生虫館. 672 (1999)

吉村健太郎：“日本寄生虫学研究第 6 卷”目黑寄生虫博物馆基金会 672（1999）。