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

Skorska A, von Haehling S, Ludwig M, Lux CA, Gaebel R, Kleiner G, Klopsch C, Dong J, Curato C, Altarche-Xifró W, Slavic S, Unger T, Steinhoff G, Li J, David R - J. Cell. Mol. Med. (2015)

Bottom Line: 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.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.Our results indicate CD4(+) AT2R(+) cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.

View Article: PubMed Central - PubMed

Affiliation: Reference and Translation Centre for Cardiac Stem Cell Therapy (RTC)/Department of Cardiac Surgery, University of Rostock, Rostock, Germany.

No MeSH data available.


Related in: MedlinePlus

CD4+AT2R+ T cells were reduced in HF patients (A) *P < 0.05 (heart failure, n = 9, healthy donors, n = 27). (B) Representative FACS plots from healthy controls (upper panel) and HF patients (lower panel).
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fig01: CD4+AT2R+ T cells were reduced in HF patients (A) *P < 0.05 (heart failure, n = 9, healthy donors, n = 27). (B) Representative FACS plots from healthy controls (upper panel) and HF patients (lower panel).

Mentions: The baseline characteristics of patients with HF are presented in Table S1. A CD4+ AT2R+ T cell population was detected by flow cytometry in mononuclear cells isolated from peripheral blood of both patients with HF (Fig. S1A) and healthy controls. AT2R expression was confirmed on mRNA level (Fig. S1B). To study the adaptive distribution of CD4+ AT2R+ T cells during cardiac injury, we compared the frequency of these cells in peripheral blood of patients with HF with those of healthy controls. The frequency of CD4+ AT2R+ T cells in blood CD4+ T cells was reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients with HF (Fig.1A), revealing a potential accumulation of CD4+ AT2R+ T cells infiltrating the failing heart. As a result of the essential role of regulatory T cells (Treg) in controlling immune response under physiological and pathological conditions, we have addressed the expression of immunoregulatory transcription factor FoxP3, Treg surface marker CD25 within the CD4+ AT2R+ T cell subset, and the potential to produce anti-inflammatory IL-10 cytokine. In human CD4+ AT2R+ T cells, the frequency of FoxP3-positive cells was increased by 2.1-fold (Fig.2, P < 0.0001), the frequency of IL-10-secreting cells was increased by 12.6-fold (healthy donors) and 41.2-fold (HF) compared to CD4+ AT2R− T cells (P < 0.01, P < 0.05, respectively; Fig.2B and C). However, no difference in CD25 expression was detected (Fig.2, right plot).


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

Skorska A, von Haehling S, Ludwig M, Lux CA, Gaebel R, Kleiner G, Klopsch C, Dong J, Curato C, Altarche-Xifró W, Slavic S, Unger T, Steinhoff G, Li J, David R - J. Cell. Mol. Med. (2015)

CD4+AT2R+ T cells were reduced in HF patients (A) *P < 0.05 (heart failure, n = 9, healthy donors, n = 27). (B) Representative FACS plots from healthy controls (upper panel) and HF patients (lower panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549048&req=5

fig01: CD4+AT2R+ T cells were reduced in HF patients (A) *P < 0.05 (heart failure, n = 9, healthy donors, n = 27). (B) Representative FACS plots from healthy controls (upper panel) and HF patients (lower panel).
Mentions: The baseline characteristics of patients with HF are presented in Table S1. A CD4+ AT2R+ T cell population was detected by flow cytometry in mononuclear cells isolated from peripheral blood of both patients with HF (Fig. S1A) and healthy controls. AT2R expression was confirmed on mRNA level (Fig. S1B). To study the adaptive distribution of CD4+ AT2R+ T cells during cardiac injury, we compared the frequency of these cells in peripheral blood of patients with HF with those of healthy controls. The frequency of CD4+ AT2R+ T cells in blood CD4+ T cells was reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients with HF (Fig.1A), revealing a potential accumulation of CD4+ AT2R+ T cells infiltrating the failing heart. As a result of the essential role of regulatory T cells (Treg) in controlling immune response under physiological and pathological conditions, we have addressed the expression of immunoregulatory transcription factor FoxP3, Treg surface marker CD25 within the CD4+ AT2R+ T cell subset, and the potential to produce anti-inflammatory IL-10 cytokine. In human CD4+ AT2R+ T cells, the frequency of FoxP3-positive cells was increased by 2.1-fold (Fig.2, P < 0.0001), the frequency of IL-10-secreting cells was increased by 12.6-fold (healthy donors) and 41.2-fold (HF) compared to CD4+ AT2R− T cells (P < 0.01, P < 0.05, respectively; Fig.2B and C). However, no difference in CD25 expression was detected (Fig.2, right plot).

Bottom Line: 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.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.Our results indicate CD4(+) AT2R(+) cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.

View Article: PubMed Central - PubMed

Affiliation: Reference and Translation Centre for Cardiac Stem Cell Therapy (RTC)/Department of Cardiac Surgery, University of Rostock, Rostock, Germany.

No MeSH data available.


Related in: MedlinePlus