| First Author | Sur M | Year | 2023 |
| Journal | Cells | Volume | 12 |
| Issue | 19 | PubMed ID | 37830560 |
| Mgi Jnum | J:349822 | Mgi Id | MGI:7541805 |
| Doi | 10.3390/cells12192346 | Citation | Sur M, et al. (2023) Transgenic Mice Expressing Functional TCRs Specific to Cardiac Myhc-alpha 334-352 on Both CD4 and CD8 T Cells Are Resistant to the Development of Myocarditis on C57BL/6 Genetic Background. Cells 12(19) |
| abstractText | Myocarditis is a predominant cause of congestive heart failure and sudden death in children and young adolescents that can lead to dilated cardiomyopathy. Lymphocytic myocarditis mediated by T cells can result from the recognition of cardiac antigens that may involve CD4 or CD8 T cells or both. In this report, we describe the generation of T cell receptor (TCR) transgenic mice on a C57BL/6 genetic background specific to cardiac myosin heavy chain (Myhc)-alpha 334-352 and make the following observations: First, we verified that Myhc-alpha 334-352 was immunogenic in wild-type C57BL/6 mice and induced antigen-specific CD4 T cell responses despite being a poor binder of IA(b); however, the immunized animals developed only mild myocarditis. Second, TCRs specific to Myhc-alpha 334-352 in transgenic mice were expressed in both CD4 and CD8 T cells, suggesting that the expression of epitope-specific TCR is common to both cell types. Third, although T cells from naive transgenic mice did not respond to Myhc-alpha 334-352, both CD4 and CD8 T cells from animals immunized with Myhc-alpha 334-352 responded to the peptide, indicating that antigen priming is necessary to break tolerance. Fourth, although the transgenic T cells could produce significant amounts of interferon-gamma and interleukin-17, the immunized animals developed only mild disease, indicating that other soluble factors might be necessary for developing severe myocarditis. Alternatively, the C57BL/6 genetic background might be a major contributing factor for resistance to the development of myocarditis. Taken together, our model permits the determination of the roles of both CD4 and CD8 T cells to understand the disease-resistance mechanisms of myocarditis in a single transgenic system antigen-specifically. |
