Regulatory T cells ameliorate cardiac remodeling after myocardial infarction

2011 ◽  
Vol 107 (1) ◽  
Author(s):  
Ting-Ting Tang ◽  
Jing Yuan ◽  
Zheng-Feng Zhu ◽  
Wen-Cai Zhang ◽  
Hong Xiao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cardiac Remodeling

scholarly journals Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Zhipeng Zeng ◽  
Kunwu Yu ◽  
Long Chen ◽  
Weihua Li ◽  
Hong Xiao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Interleukin 2 ◽  
Treg Cells ◽  
Left Ventricular ◽  
Border Zone ◽  
Infarcted Myocardium

CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV) function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th) cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

scholarly journals Circulating Th17 and Tc17 Cells and Their Imbalance with Regulatory T Cells Is Associated with Myocardial Infarction in Young Indian Patients

2015 ◽  
Vol 05 (12) ◽  
pp. 373-387 ◽  
Author(s):  
Thiruvelselvan Ponnusamy ◽  
Komarlu Venkatachala Srikanth ◽  
Ramanjappa Manjunatha ◽  
Vijay V. Kakkar ◽  
Lakshmi Mundkur
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Indian Patients ◽  
Tc17 Cells

scholarly journals CD8+T-cells negatively regulate inflammation post-myocardial infarction

2019 ◽  
Vol 317 (3) ◽  
pp. H581-H596 ◽  
Author(s):  
Daria V. Ilatovskaya ◽  
Cooper Pitts ◽  
Joshua Clayton ◽  
Mark Domondon ◽  
Miguel Troncoso ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Cardiac Remodeling ◽  
Scar Formation ◽  
Post Myocardial Infarction ◽  
Cardiac Rupture ◽  
Necrotic Tissue ◽  
Cardiac Physiology ◽  
Wild Type ◽  
Delayed Removal

The adaptive immune response is key for cardiac wound healing post-myocardial infarction (MI) despite low T-cell numbers. We hypothesized that CD8+T-cells regulate the inflammatory response, leading to decreased survival and cardiac function post-MI. We performed permanent occlusion of the left anterior descending coronary artery on C57BL/6J and CD8atm1makmice (deficient in functional CD8+T-cells). CD8atm1makmice had increased survival at 7 days post-MI compared with that of the wild-type (WT) and improved cardiac physiology at day 7 post-MI. Despite having less mortality, 100% of the CD8atm1makgroup died because of cardiac rupture compared with only 33% of the WT. Picrosirius red staining and collagen immunoblotting indicated an acceleration of fibrosis in the infarct area as well as remote area in the CD8atm1makmice; however, this increase was due to elevated soluble collagen implicating poor scar formation. Plasma and tissue inflammation were exacerbated as indicated by higher levels of Cxcl1, Ccl11, matrix metalloproteinase (MMP)-2, and MMP-9. Immunohistochemistry and flow cytometry indicated that the CD8atm1makgroup had augmented numbers of neutrophils and macrophages at post-MI day 3 and increased mast cell markers at post-MI day 7. Cleavage of tyrosine-protein kinase MER was increased in the CD8atm1makmice, resulting in delayed removal of necrotic tissue. In conclusion, despite having improved cardiac physiology and overall survival, CD8atm1makmice had increased innate inflammation and poor scar formation, leading to higher incidence of cardiac rupture. Our data suggest that the role of CD8+T-cells in post-MI recovery may be both beneficial and detrimental to cardiac remodeling and is mediated via a cell-specific mechanism.NEW & NOTEWORTHY We identified new mechanisms implicating CD8+T-cells as regulators of the post-myocardial infarction (MI) wound healing process. Mice without functional CD8+T-cells had improved cardiac physiology and less mortality 7 days post MI compared with wild-type animals. Despite having better overall survival, animals lacking functional CD8+T-cells had delayed removal of necrotic tissue, leading to poor scar formation and increased cardiac rupture, suggesting that CD8+T-cells play a dual role in the cardiac remodeling process.

Frequency of naturally-occurring regulatory T cells is reduced in patients with ST-segment elevation myocardial infarction

2007 ◽  
Vol 120 (4) ◽  
pp. 631-634 ◽  
Author(s):  
Gennaro Sardella ◽  
Leonardo De Luca ◽  
Vittorio Francavilla ◽  
Daniele Accapezzato ◽  
Massimo Mancone ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
Naturally Occurring ◽  
St Segment

Abstract 211: Regulatory T cells improve healing after myocardial infarction

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Stefan Frantz ◽  
Johannes Weirather ◽  
Benjamin Vogel ◽  
Niklas Beyersdorf ◽  
Thomas Kerkau ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cd4 T Cells ◽  
Matched Control ◽  
Coagulation Factor ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Control Group

Background: The proinflammatory activation of innate immunity by myocardial ischemic injury has been recognized for long time. Our recent data have indicated that activation of CD4+ T cells, presumably by auto-antigen recognition, is a prerequisite for formation of a stable scar and prevention from left ventricular dilation after experimental myocardial infarction in mice. We here hypothesized that regulatory CD4+CD25+Foxp3+CD4+ T cells might improve left ventricular wound healing and prevent from adverse remodeling after myocardial infarction. Results: Experimental myocardial infarction in mice induced the proliferation and activation of CD4+CD25+Foxp3+ regulatory T cells, as demonstrated by intracellular expression of the Ikaros family transcription factor Helios, in heart draining lymph nodes. Pretreatment of mice with an anti-CD25 antibody before myocardial infarction efficiently depleted CD4+CD25+Foxp3+ regulatory T cells and increased mortality after myocardial infarction as compared to mice treated with an isotype-matched control antibody of irrelevant specificity, i.e., 25% survival in anti-CD25 treated mice vs. 55,9% survival in control antibody treated animals. Therapeutic activation of regulatory CD4+CD25+Foxp3+ T cells by a superagonistic anti-CD28 antibody (CD28-SA) applied at day 2 after myocardial infarction prevented, compared to mice treated with an isotype-matched control antibody, from left ventricular rupture and resulted in improved survival (47.1% survival in the control group vs. 76.6% survival in the CD28-SA treated group). CD28-SA treatment lead to expansion of CD4+CD25+Foxp3+ T-cells in the peripheral blood and increased their frequency in the infarcted myocardium. This was associated with increased expression of several molecules known to facilitate wound healing by promoting the formation of a stable scar such as osteopontin and coagulation factor XIII. Conclusion: CD4+CD25+Foxp3+ regulatory T-cells are a prerequisite for proper myocardial wound healing and can be therapeutically activated to improve outcome after experimental myocardial infarction.

scholarly journals A2bR-dependent signaling alters immune cell composition and enhances IL-6 formation in the ischemic heart

2019 ◽  
Vol 317 (1) ◽  
pp. H190-H200 ◽  
Author(s):  
Christina Alter ◽  
Zhaoping Ding ◽  
Ulrich Flögel ◽  
Jürgen Scheller ◽  
Jürgen Schrader
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Nk Cells ◽  
Immune Cells ◽  
Cardiac Remodeling ◽  
Immune Cell ◽  
Ischemic Heart ◽  
Cell Composition ◽  
Immune Cell Subsets

Although the cardioprotective effect of adenosine is undisputed, the role of the adenosine A2breceptor (A2bR) in ischemic cardiac remodeling is not defined. In this study we aimed to unravel the role A2bR plays in modulating the immune response and the healing mechanisms after myocardial infarction. Genetic and pharmacological (PSB603) inactivation of A2bR as well as activation of A2bR with BAY60-6583 does not alter cardiac remodeling of the infarcted (50-min left anterior descending artery occlusion/reperfusion) murine heart. Flow cytometry of immune cell subsets identified a significant increase in B cells, NK cells, CD8 and CD4 T cells, as well as FoxP3-expressing regulatory T cells in the injured heart in A2bR-deficient mice. Analysis of T-cell function revealed that expression and secretion of interleukin (IL)-2, interferon (IFN)γ, and tumor necrosis factor (TNF)α by T cells is under A2bR control. In addition, we found substantial cellular heterogeneity in the response of immune cells and cardiomyocytes to A2bR deficiency: while in the absence of A2bR, expression of IL-6 was greatly reduced in cardiomyocytes and immune cells except T cells, and expression of IL-1β was strongly reduced in cardiomyocytes, granulocytes, and B cells as determined by quantitative PCR. Our findings indicate that A2bR signaling in the ischemic heart triggers substantial changes in cardiac immune cell composition of the lymphoid lineage and induces a profound cell type-specific downregulation of IL-6 and IL-1β. This suggests the presence of a targetable adenosine–A2bR–IL-6-axis triggered by adenosine formed by the ischemic heart.NEW & NOTEWORTHY Genetic deletion and pharmacological inactivation/activation of A2bR does not alter cardiac remodeling after MI but is associated by compensatory upregulation of various pro- and anti-inflammatory immune cell subsets (B cells, NK cells, CD8 and CD4 T cells, regulatory T cells). In the inflamed heart, A2bR modulates the expression of IL-2, IFNγ, TNFα in T cells and of IL-6 in cardiomyocytes, monocytes, granulocytes and B cells. This suggests an important adenosine–IL-6 axis, which is controlled by A2bR via local adenosine.

Exosomes derived from regulatory T cells ameliorate acute myocardial infarction by promoting macrophage M2 polarization

IUBMB Life ◽  
2020 ◽  
Vol 72 (11) ◽  
pp. 2409-2419
Author(s):  
Hao Hu ◽  
Jiawei Wu ◽  
Cheng Cao ◽  
Likun Ma
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
M2 Polarization

Update on the Protective Role of Regulatory T Cells in Myocardial Infarction

2016 ◽  
Vol 68 (6) ◽  
pp. 401-413 ◽  
Author(s):  
Abdullah Kaplan ◽  
Raffaele Altara ◽  
Ali Eid ◽  
George W. Booz ◽  
Fouad A. Zouein
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Protective Role

scholarly journals Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Serena Zacchigna ◽  
Valentina Martinelli ◽  
Silvia Moimas ◽  
Andrea Colliva ◽  
Marco Anzini ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cardiomyocyte Proliferation ◽  
Paracrine Effect
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