The CD4(+) AT2R(+) T cell subpopulation improves post-infarction remodelling and restores cardiac function

Area of Science:

• Immunology
• Cardiology
• Regenerative Medicine

Background:

• Myocardial infarction (MI) frequently leads to heart failure (HF).
• The renin-angiotensin system (RAS), particularly angiotensin II (Ang II), influences cardiac injury and repair through AT1 and AT2 receptors (AT1R, AT2R).

Purpose of the Study:

• To investigate the mechanisms linking the RAS to immune cells in the context of HF.
• To characterize the role of CD4(+) AT2R(+) T cells in cardiac repair post-MI.

Main Methods:

• Flow cytometry was used to analyze immune cell populations in a rodent model of HF and in human HF patients.
• Functional assessment involved intramyocardial injection of CD4(+) AT2R(+) T cells into recipient rats with MI.
• Characterization of CD4(+) AT2R(+) T cells included analysis of regulatory markers (FoxP3) and cytokine secretion (interleukin-10).

Main Results:

• Increased CD4(+) AT2R(+) T cells were found in the rat heart and spleen post-MI, but decreased in peripheral blood, a trend also observed in HF patients.
• These CD4(+) AT2R(+) T cells exhibited regulatory properties, expressing FoxP3 and secreting interleukin-10.
• Transplantation of MI-induced splenic CD4(+) AT2R(+) T cells into recipient rats reduced infarct size and improved cardiac performance.

Conclusions:

• CD4(+) AT2R(+) T cells represent a T cell subset that enhances heart function and reduces infarction size following MI.
• These findings suggest CD4(+) AT2R(+) cells hold promise for regenerative therapy strategies, including cell transplantation or AT2R activation.