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-

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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.