Veterinary and Biomedical Sciences, Department of
Document Type
Article
Date of this Version
9-25-2023
Citation
Sur, M.; Rasquinha, M.T.; Arumugam, R.; Massilamany, C.; Gangaplara, A.; Mone, K.; Lasrado, N.; Yalaka, B.; Doiphode, A.; Gurumurthy, C.; et al. Transgenic Mice Expressing Functional TCRs Specific to Cardiac Myhc-α 334–352 on Both CD4 and CD8 T Cells Are Resistant to the Development of Myocarditis on C57BL/6 Genetic Background. Cells 2023, 12, 2346. https://doi.org/10.3390/ cells12192346
Abstract
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)-α 334–352 and make the following observations: First, we verified that Myhc-α 334–352 was immunogenic in wild-type C57BL/6 mice and induced antigen-specific CD4 T cell responses despite being a poor binder of IAb; however, the immunized animals developed only mild myocarditis. Second, TCRs specific to Myhc-α 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 naïve transgenic mice did not respond to Myhc-α 334–352, both CD4 and CD8 T cells from animals immunized with Myhc-α 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- 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.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Immunology and Infectious Disease Commons, Medical Sciences Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Pathology and Pathobiology Commons
Comments
Open access.