| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with Coxsackievirus B3 (CB3) or Encephalo-Myocarditis Virus (EMV). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3- or EMV-infected nu/+mice. Acute myocarditis occurred in both nu/nu and nu/+ mice, Severe myocarditis, however, developed only in nu/+ and nu/nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and
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nu/nu mice reconstituted with CB3-sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogesis of ongoing myocarditis.
To test the effects of interleukinー2 (IL-2) upon CB3 myocarditis recombinant human IL-2, 5x10^4U, was administered subcutaneously daily starting on day O and on day 7 for 7 days, respectively. The treated groups were compared to infected controls. As a result, IL-2 has differential effects upon CB3 myocarditis ; IL-2 has the potency to limit CB3 myocarditis in the acute viremic stage, but it aggravates the course and the severity of the disease in the subacute a viremic stage by T cell activation. Also, FK-506, a novel immunosuppressant, induced immunosuppression in CB3 myocarditis, associated with a high mortality, notwithstanding the reduction of cardiac pathology.
In addition, Fc receptor-mediated CB3 infection in vitro and in vivo was demonstrated in this murine model. Less
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