{"doi":"10.3390/cells12192346","title":"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","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-γ 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.","journal":"Cells","year":2023,"id":355168,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":648038,"name":"Mahima T. Rasquinha","orcid":"0000-0003-0923-4869","position":1,"is_corresponding":false},{"id":494190,"name":"Rajkumar Arumugam","orcid":"0000-0002-7021-7884","position":2,"is_corresponding":false},{"id":494192,"name":"Chandirasegaran Massilamany","orcid":"0000-0002-0205-282X","position":3,"is_corresponding":false},{"id":888714,"name":"Arunkumar Gangaplara","orcid":null,"position":4,"is_corresponding":false},{"id":1053129,"name":"Kiruthiga Mone","orcid":"0000-0003-0379-4152","position":5,"is_corresponding":false},{"id":494191,"name":"Ninaad Lasrado","orcid":"0000-0001-6762-2654","position":6,"is_corresponding":false},{"id":494924,"name":"Bharathi Yalaka","orcid":null,"position":7,"is_corresponding":false},{"id":1103584,"name":"Aakash Doiphode","orcid":null,"position":8,"is_corresponding":false},{"id":391888,"name":"Channabasavaiah B. Gurumurthy","orcid":null,"position":9,"is_corresponding":false},{"id":494195,"name":"David Steffen","orcid":"0000-0002-5166-2296","position":10,"is_corresponding":false},{"id":494196,"name":"Jay Reddy","orcid":"0000-0003-4082-9254","position":11,"is_corresponding":false},{"id":648039,"name":"Meghna Sur","orcid":"0000-0003-0878-4930","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:13:16.394812Z","pmid":"37830560","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}