Key result
Distinct oligoclonal accumulation of TCR Vbeta1, 10, and 13 T cells occurred in normal donor hearts transplanted into mice with chronic myocarditis, indicating an autoimmune mechanism.
Why the study?
Does an autoimmune response involving specific T cell clonotypes mediate the progression of chronic ongoing myocarditis in a murine model?
Does an autoimmune response involving specific T cell clonotypes mediate the progression of chronic ongoing myocarditis in a murine model?
Specific T cell clonotypes (TCR Vbeta1, 10, and 13) accumulate in transplanted normal hearts in mice with chronic myocarditis, suggesting an autoimmune mechanism drives the progression of the disease.
Answers are grounded in this paper and cite their sources.
Supports autoimmune T-cell mediation of murine chronic myocarditis; leaves open human translation and therapeutic targeting.
Autoimmne mechanisms have been implicated in the pathogenesis of chronic ongoing mycarditis. An earlier study of murine chronic ongoing myocarditis reported that infiltrating T cells and macrophages were prominent in the normal donor heart, in a heterotopic cardiac transplantation model. It was demonstrated that myocarditis was transferred to a normal heart transplanted into a mouse with chronic myocarditis. The present study investigated an autoimmune link to the pathogenesis of chronic ongoing myocarditis by analyzing the T cell clonalities in the model. To characterize the accumulating T cells in the donor heart, the T cell receptor beta genes (TCRBG) were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) from mRNA in the donor hearts and accumulating TCRBG clonotypes were contrasted with those from recipient hearts. Inbred 3-week-old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain), 2 x 10(4) PFU, and housed for more than 60 days. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis, as well as into the mice with chronic ongoing myocarditis. Both recipient and donor hearts were evaluated histologically 2 weeks after the transplantation. TCRBG were amplified by RT-PCR from mRNA of recipient and donor hearts and spleens. The specific accumulating TCRBG clonotypes were identified by their single strand conformation polymorphism. Multiple clonotypic accumulations occurred in the donor heart after cardiac transplantation. Distinct oligoclonal accumulation of TCR Vbeta1, 10, and 13 T cells was found in both recipient and donor hearts in 3 of 4 mice. Moreover, these clonotypes were not observed in spleen cells of the recipient mice. T specific cells expanding clonotypes of TCRBG are responsible for transferring myocarditis to the donor heart. An autoimmune response may, therefore, play a key role in the progression of chronic ongoing myocarditis.
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Nakamura et al. (2001) studied Chronic ongoing myocarditis (n=12). Heterotopic cardiac transplantation vs. Normal A/J mouse hearts transplanted into normal mice was evaluated on T cell receptor beta gene (TCRBG) clonotypes in donor and recipient hearts. Distinct oligoclonal accumulation of TCR Vbeta1, 10, and 13 T cells occurred in normal donor hearts transplanted into mice with chronic myocarditis, indicating an autoimmune mechanism.
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