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Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

Zhu ZF, Meng K, Zhong YC, Qi L, Mao XB, Yu KW, Zhang W, Zhu PF, Ren ZP, Wu BW, Ji QW, Wang X, Zeng QT - PLoS ONE (2014)

Bottom Line: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls.The serum levels of IL-10 were similar between the two cohorts.A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT

Objective: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS.

Methods: One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction.

Results: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts.

Conclusions: A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

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Related in: MedlinePlus

Frequencies of CD4+LAP+ Tregs in freshly isolated PBMCs from patients with CPS (n = 32), CSA (n = 18), and ACS (n = 44,AMI (n = 16) and UA (n = 28)).(A) Representative FSC/SSC dot plot shows the gated CD4+ T cells. (B) Representative FACS analyses of a sample from each group show the frequencies of CD4+LAP+ Tregs (upper panels show isotype controls). (C) Percentages of CD4+LAP+ Tregs based on FACs analyses were comparable among ACS, CSA, and CPS groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
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pone-0088775-g002: Frequencies of CD4+LAP+ Tregs in freshly isolated PBMCs from patients with CPS (n = 32), CSA (n = 18), and ACS (n = 44,AMI (n = 16) and UA (n = 28)).(A) Representative FSC/SSC dot plot shows the gated CD4+ T cells. (B) Representative FACS analyses of a sample from each group show the frequencies of CD4+LAP+ Tregs (upper panels show isotype controls). (C) Percentages of CD4+LAP+ Tregs based on FACs analyses were comparable among ACS, CSA, and CPS groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.

Mentions: We determined the frequency of circulating CD4+LAP+ Tregs using flow cytometry. We found that the percentage of circulating CD4+LAP+ Tregs in the CD4+ T cell population was decreased significantly in patients with ACS (0.68±0.04%) compared to patients with CSA (1.2±0.12%) or CPS (1.45±0.14%) (p<0.001) as shown in Figure 2. There was no obvious difference between the CSA and CPS groups (p = 0.21).


Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

Zhu ZF, Meng K, Zhong YC, Qi L, Mao XB, Yu KW, Zhang W, Zhu PF, Ren ZP, Wu BW, Ji QW, Wang X, Zeng QT - PLoS ONE (2014)

Frequencies of CD4+LAP+ Tregs in freshly isolated PBMCs from patients with CPS (n = 32), CSA (n = 18), and ACS (n = 44,AMI (n = 16) and UA (n = 28)).(A) Representative FSC/SSC dot plot shows the gated CD4+ T cells. (B) Representative FACS analyses of a sample from each group show the frequencies of CD4+LAP+ Tregs (upper panels show isotype controls). (C) Percentages of CD4+LAP+ Tregs based on FACs analyses were comparable among ACS, CSA, and CPS groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928284&req=5

pone-0088775-g002: Frequencies of CD4+LAP+ Tregs in freshly isolated PBMCs from patients with CPS (n = 32), CSA (n = 18), and ACS (n = 44,AMI (n = 16) and UA (n = 28)).(A) Representative FSC/SSC dot plot shows the gated CD4+ T cells. (B) Representative FACS analyses of a sample from each group show the frequencies of CD4+LAP+ Tregs (upper panels show isotype controls). (C) Percentages of CD4+LAP+ Tregs based on FACs analyses were comparable among ACS, CSA, and CPS groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
Mentions: We determined the frequency of circulating CD4+LAP+ Tregs using flow cytometry. We found that the percentage of circulating CD4+LAP+ Tregs in the CD4+ T cell population was decreased significantly in patients with ACS (0.68±0.04%) compared to patients with CSA (1.2±0.12%) or CPS (1.45±0.14%) (p<0.001) as shown in Figure 2. There was no obvious difference between the CSA and CPS groups (p = 0.21).

Bottom Line: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls.The serum levels of IL-10 were similar between the two cohorts.A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT

Objective: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS.

Methods: One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction.

Results: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts.

Conclusions: A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Show MeSH
Related in: MedlinePlus