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

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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