Open AccessThe CD 4 + AT 2R + T cell subpopulation improves post‐infarction remodelling and restores cardiac function
Author(s) -
Skorska Anna,
Haehling Stephan,
Ludwig Marion,
Lux Cornelia A.,
Gaebel Ralf,
Kleiner Gabriela,
Klopsch Christian,
Dong Jun,
Curato Caterina,
AltarcheXifró Wassim,
Slavic Svetlana,
Unger Thomas,
Steinhoff Gustav,
Li Jun,
David Robert
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12574
Subject(s) - myocardial infarction , heart failure , spleen , immune system , angiotensin ii , cardiac function curve , medicine , t cell , receptor , endocrinology , ventricular remodeling , foxp3 , immunology , biology
Myocardial infarction ( MI ) is a major condition causing heart failure ( HF ). After MI , the renin angiotensin system ( RAS ) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT 1 and AT 2 receptors ( AT 1R, AT 2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD 4 + AT 2R + cells in the rat heart and spleen post‐infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD 4 + AT 2R + T cells in circulating blood, post‐infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD 4 + cells. CD 4 + AT 2R + T cells within blood CD 4 + T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD 4 + AT 2R + T cells which expressed regulatory FoxP3, secreted interleukin‐10 and other inflammatory‐related cytokines. Furthermore, intramyocardial injection of MI ‐induced splenic CD 4 + AT 2R + T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD 4 + AT 2R + cells as a T cell subset improving heart function post‐ MI corresponding with reduced infarction size in a rat MI ‐model. Our results indicate CD 4 + AT 2R + cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT 2R activation or a combination thereof.