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

Anna Skorska, Stephan von Haehling, Marion Ludwig, Cornelia A. Lux, Ralf Gaebel, Gabriela Kleiner, Christian Klopsch, Jun Dong, Caterina Curato, Wassim Altarche-Xifro, Svetlana Slavic, Thomas Unger, Gustav Steinhoff, Jun Li, Robert David*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.? 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Original languageEnglish
Pages (from-to)1975-1985
JournalJournal of Cellular and Molecular Medicine
Issue number8
Publication statusPublished - Aug 2015


  • angiotensin II type 2 receptor
  • renin angiotensin system
  • CD4(+) lymphocytes
  • myocardial infarction
  • heart failure cardiac remodelling

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