Tissue-Resident Memory T Cells in the Heart: An Emerging Role in Chronic Inflammation

Area of Science:

• Immunology
• Cardiology
• Molecular Biology

Background:

• T lymphocytes are key regulators of cardiac inflammation in conditions like myocardial infarction and heart failure.
• Cardiac T cell responses are increasingly understood as antigen-driven and sustained, not just transient.
• Alpha-myosin heavy chain (α-MyHC) is a dominant cardiac autoantigen triggering pathogenic T cell responses.

Purpose of the Study:

• To propose that cardiac injury leads to antigen-specific T cells acquiring tissue-resident phenotypes in the myocardium.
• To link acute immune activation to chronic, relapsing cardiac inflammation.
• To highlight the role of α-MyHC-specific tissue-resident memory T cells (Trm) in cardiac autoimmunity.

Main Methods:

• Review of existing literature on T cell roles in cardiac homeostasis and disease.
• Analysis of Trm characteristics, developmental pathways, and presence in the heart.
• Integration of evidence for α-MyHC-specific Trm in cardiac autoimmunity and immunotherapy adverse events.

Main Results:

• Cardiac injury can establish antigen-specific T cell populations within the myocardium.
• Tissue-resident memory T cells (Trm) are implicated in chronic cardiac inflammation.
• α-MyHC-specific Trm are potential drivers of cardiac autoimmunity and myocarditis.

Conclusions:

• A framework is proposed where cardiac injury seeds persistent, resident T cell populations.
• This persistence links acute events to chronic, relapsing cardiac inflammation.
• Understanding Trm is crucial for developing targeted therapies for chronic cardiac inflammation.