Myocardial aging as a T-cell–mediated phenomenon
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Significance: Aging is a risk factor for heart diseases, and it is also known to impact on several immunological processes. Nevertheless, most studies addressing the cardio-immune cross-talk have focused on juvenile rather than senescent animal models. In the present study, we addressed this gap and found that immunological activity contributes to myocardial aging. By using different lymphocyte-deficient animal models and heterochronic adoptive cell-transfer protocols, our study revealed a pivotal role for CD4 + T cells in mediating spontaneous local inflammation and mild organ dysfunction in aged hearts. These results might shed new light on the emerging field of “immunocardiology” because they reveal that spontaneous heart-directed immune responses arise even in the absence of previous myocardial tissue damage.
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Accumulation of activated memory cardiac T cells in the mediastinal lymph node and myocardium is associated with myocardial aging, leading to significantly lower cardiac output.
“Another investigation demonstrated that the accumulation of activated memory cardiac T cells in the mediastinal lymph node and myocardium is associated with myocardial aging, leading to significantly lower cardiac output. 271,300,301”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [271]
The sections on spontaneous CD4+ T-cell activation and immune–somatic factors report activated effector-memory T cells in the mediastinal lymph nodes of aged mice and increased myocardial infiltration by T cells from aged donors. The myocardial-aging results report significantly reduced fractional shortening, not significantly lower cardiac output. The paper also says those T cells alone did not cause major cardiac alterations, so the claim overstates their causal effect. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAged mice harbor a significantly higher number of α-MyHC-specific T cells within the heart and an increased number of IFNγ-producing T cells in heart-draining lymph nodes compared with young adult mice.
“Animal studies have shown that aged mice harbor a significantly higher number of α -MyHC-specific T cells within the heart and an increased number of IFNγ -producing T cells in heart-draining lymph nodes compared with young adult mice. 42,271”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [271]
The section on spontaneous T-cell activation in mediastinal lymph nodes (page unavailable) reports an age-related increase in activated CD4+ T cells in heart-draining nodes; the paper also reports accumulation of IFN-γ-producing effector CD4+ T cells there. It does not establish that aged mice have significantly more α-MyHC-specific T cells within their hearts than young mice. Its myosin-specific finding concerns antibodies, not T cells. (LLM, conf=0.88)
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- Authors
- Ramos, G. C., van den Berg, A., Nunes-Silva, V., Weirather, J., Peters, L., Burkard, M., Friedrich, M., Pinnecker, J., Abeßer, M., Heinze, K. G., Schuh, K., Beyersdorf, N., Kerkau, T., Demengeot, J., Frantz, S., & Hofmann, U.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- Comprehensive Heart Failure Center, University Clinic Wuerzburg, D-97078 Wuerzburg, Germany;
- Instituto Gulbenkian de Ciência, PT-2781-901 Oeiras, Portugal;
- University of Würzburg (DE)
- Instituto Gulbenkian de Ciência (PT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-03-02
- Volume
- 114
- Issue
- 12
- Pages
- E2420-E2429
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5373357
- OpenAlex
- W2592528608
- Cited by
- 168
- References
- 61
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 21 · 2023: 19 · 2022: 23 · 2021: 19 · 2020: 27 · 2019: 12 · 2018: 13 · 2017: 8
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development) (245856/2012-9)
- Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) (BMBF01 EO1004)
- Deutsche Forschungsgemeinschaft (DFG) (SFB688)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cardiac aging, T cells, mediastinal lymph nodes, adoptive T cell therapy, cardiac function decline
- MeSH terms
- Aging, Animals, Heart, Humans, Lymph Nodes, Male, Mice, Inbred C57BL, Myocardium, CD4-Positive T-Lymphocytes, Adoptive Transfer, Mice
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