The CD4+AT2R+ T cell subpopulation improves post‐infarction remodelling and restores cardiac function

Journal of Cellular and Molecular Medicine

Anna Skorska⁴  Stephan von Haehling³  Marion Ludwig⁴  Cornelia A. Lux⁴  Ralf Gaebel⁴  Gabriela Kleiner⁴  Christian Klopsch⁴  Jun Dong¹  Caterina Curato²  Wassim Altarche-Xifró²  Svetlana Slavic²  Thomas Unger²  Gustav Steinhoff⁴  Jun Li⁴ 

[1] German Rheumatism Research Centre, Berlin, Germany;Center for Cardiovascular Research (CCR) and Institute of Pharmacology, Charité - Universitätsmedizin Berlin, Berlin, Germany;Center for Cardiovascular Research and Department of Cardiology, Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, Berlin, Germany;Reference and Translation Centre for Cardiac Stem Cell Therapy (RTC)/Department of Cardiac Surgery, University of Rostock, Rostock, Germany

关键词: angiotensin II type 2 receptor;    renin angiotensin system;    CD4+ lymphocytes;    myocardial infarction;    heart failure cardiac remodelling;   

DOI  :  10.1111/jcmm.12574

来源: Wiley

【 摘 要 】

Abstract

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 AT1 and AT2 receptors (AT1R, AT2R). 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 CD4⁺ AT2R⁺ 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 CD4⁺ AT2R⁺ 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 CD4⁺ cells. CD4⁺ AT2R⁺ T cells within blood CD4⁺ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4⁺ AT2R⁺ T cells which expressed regulatory FoxP3, secreted interleukin-10 and other inflammatory-related cytokines. Furthermore, intramyocardial injection of MI-induced splenic CD4⁺ AT2R⁺ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4⁺ AT2R⁺ cells as a T cell subset improving heart function post-MI corresponding with reduced infarction size in a rat MI-model. Our results indicate CD4⁺ AT2R⁺ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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