Molecular immunological study on host morbidity of mice infected with Angiostrongylus cantonensis. -Analysis of the mechanisms of CD4^+T-cell-dependent body weight reduction and neurological symptoms-

不同品系的小鼠对广州管圆线虫感染的易感性和宿主发病率存在差异。感染广州管圆线虫的BALB/c小鼠的体重减轻始于感染后第15天(P.I.)是依赖于CD4^+T细胞的。因此，本研究的目的是探讨CD_4~+T细胞介导的宿主致病机制(S)在广州管圆线虫感染小鼠中的作用。结果如下：1.从感染广州管圆线虫的BALB/c小鼠15-16天的脾组织中分离出CD_4~+T细胞，诱导出广州管圆线虫抗原特异性Th1/Th2克隆。按照标准程序，这是不成功的。目前正在计划对该方法进行重大改进。2.IL-4和干扰素-γ不太可能与宿主发病率有关，因为在抗IL-4单抗治疗的小鼠和干扰素-γ基因敲除的小鼠中观察到体重减轻。3.体内注射诱导型一氧化氮合酶抑制剂氨基胍不能影响感染广州管圆线虫的BALB/c小鼠的体重变化，因此一氧化氮不参与BALB/c小鼠的宿主发病。4.从感染广州管圆线虫的BALB/c小鼠体内分离出13-20天的小鼠脾中的CD_4~+T细胞。对相对分子质量分别为56、48、40、31-22 kDa的幼虫抗原蛋白具有明显的增殖活性。5.BALB/c小鼠感染X射线照射的第三期幼虫后，虫体回收率降低，但体重减轻。提示体重减轻可能与虫体负荷量无关，而与脑内CD4~+T细胞介导的炎症反应密切相关，并伴有脑脊液中的胞浆增多。

There are murine strain dependent differences in susceptibility and host morbidity to Angiostrongylus cantonensis infection. The body weight reduction in A.cantonensis-infected BALB/c mice starting at around day 15 post-infection (p.i.) is CD4^+T cell-dependent. The aim of this study is, therefore, to determine the mechanism (s) of CD4^+T cell-mediated host morbidity of A.cantonensis-infected BALB/c strain mice. The results are as follows : 1. An attempt to induce A.cantonensis antigen specific Th1/Th2 clones from splenic CD4^+T cells separated from A.cantonensis-infected BALB/c mice at days 15-16 p.i. by the standard procedure was unsuccessful. Drastic improvement of the method is now planning. 2. It is unlikely that both IL-4 and interferon-γ are related to host morbidity, since body weight reduction was observed in mice treated with anti-IL-4 monoclonal antibody and in interferon-γ knockout mice. 3. Nitric oxide is not involved in the host morbidity in BALB/c mice, since body weight changes in A.cantonensis-infected BALB/c mice cannot be affected by the intraperitoneal administration of aminoguanidine, inhibitor of iNOS, in vivo. 4. Splenic CD4^+T cells separated from A.cantonensis-infected BALB/c mice at days 13-20 p.i. showed significant proliferative activity to young adult worm antigen proteins with molecular weights of 56, 48, 40, 31-22 kDa. 5. BALB/c mice infected with X-ray-irradiated third stage larvae yielded a lower worm recovery, but showed body weight reduction. It indicates that the body weight reduction probably is not related to the worm load, but closely associated with CD4^+T cell-mediated inflammatory responses in the brain with pleocytosis in the cerebrospinal fluid.