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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

The expression of GARP on CD4+ T cells in freshly isolated PBMCs and CD3/28-sitmulated PBMCs.Bood samples were collected from patients with CPS (n = 20), CSA (n = 17) and ACS (n = 37, AMI (n = 18), and UA (n = 19)). PBMCs were freshly isolated or stimulated with CD3/CD28 for 24 h. Then the cells were stained with anti-human CD4-FITC, anti-human GARP-PE and analyzed by flow cytometry using FACS Calibur (BD). (A) Representative dot plot shows the gated CD4+ T cells on the FSC/SSC. (B) Representative FACS images show GARP expression on CD4+ T cells in unstimulated PMBCs (upper panel) and stimulated PBMCs (lower panel) from one patient in each group. Comparison of the CD4+GARP+ T cells frequencies in unstimulated PBMCs (C) and stimulated PBMCs (D) among four groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
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pone-0088775-g003: The expression of GARP on CD4+ T cells in freshly isolated PBMCs and CD3/28-sitmulated PBMCs.Bood samples were collected from patients with CPS (n = 20), CSA (n = 17) and ACS (n = 37, AMI (n = 18), and UA (n = 19)). PBMCs were freshly isolated or stimulated with CD3/CD28 for 24 h. Then the cells were stained with anti-human CD4-FITC, anti-human GARP-PE and analyzed by flow cytometry using FACS Calibur (BD). (A) Representative dot plot shows the gated CD4+ T cells on the FSC/SSC. (B) Representative FACS images show GARP expression on CD4+ T cells in unstimulated PMBCs (upper panel) and stimulated PBMCs (lower panel) from one patient in each group. Comparison of the CD4+GARP+ T cells frequencies in unstimulated PBMCs (C) and stimulated PBMCs (D) among four groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.

Mentions: GARP is reportedly a receptor of LAP. We therefore measured the expression of GARP on CD4+ T cells. As GARP is highly expressed on activated T cells, we first stimulated PBMCs with anti-CD3/28 for 24 hours prior to the assay. GARP expression was also measured on CD4+ T cells in freshly isolated PBMCs. Figure 3 shows expression of GARP on CD4+ T cells from each patient in the study. In both stimulated and unstimulated PBMCs, the frequencies of CD4+GARP+ T cells were reduced in ACS patients compared with CSA and CPS patients. In the unstimulated condition, the frequency of circulating CD4+GARP+ T cells (CD4+GARP+ T cells/CD4+ T cells) was reduced in patients with ACS (1.15±0.10%) compared with those with CSA (1.8±0.18%) or CPS (1.91±0.19%) (p<0.005), there was no obvious difference between the CSA and CPS groups (p = 0.68). In the stimulated condition, the frequency of CD4+GARP+ T cells was also reduced in patients with ACS (4.53±0.27%) compared with CSA (6.67±0.42%) and CPS (6.73±0.65%) (p<0.005). No obvious difference was found between the CSA and CPS group (p = 0.94).


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)

The expression of GARP on CD4+ T cells in freshly isolated PBMCs and CD3/28-sitmulated PBMCs.Bood samples were collected from patients with CPS (n = 20), CSA (n = 17) and ACS (n = 37, AMI (n = 18), and UA (n = 19)). PBMCs were freshly isolated or stimulated with CD3/CD28 for 24 h. Then the cells were stained with anti-human CD4-FITC, anti-human GARP-PE and analyzed by flow cytometry using FACS Calibur (BD). (A) Representative dot plot shows the gated CD4+ T cells on the FSC/SSC. (B) Representative FACS images show GARP expression on CD4+ T cells in unstimulated PMBCs (upper panel) and stimulated PBMCs (lower panel) from one patient in each group. Comparison of the CD4+GARP+ T cells frequencies in unstimulated PBMCs (C) and stimulated PBMCs (D) among four groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0088775-g003: The expression of GARP on CD4+ T cells in freshly isolated PBMCs and CD3/28-sitmulated PBMCs.Bood samples were collected from patients with CPS (n = 20), CSA (n = 17) and ACS (n = 37, AMI (n = 18), and UA (n = 19)). PBMCs were freshly isolated or stimulated with CD3/CD28 for 24 h. Then the cells were stained with anti-human CD4-FITC, anti-human GARP-PE and analyzed by flow cytometry using FACS Calibur (BD). (A) Representative dot plot shows the gated CD4+ T cells on the FSC/SSC. (B) Representative FACS images show GARP expression on CD4+ T cells in unstimulated PMBCs (upper panel) and stimulated PBMCs (lower panel) from one patient in each group. Comparison of the CD4+GARP+ T cells frequencies in unstimulated PBMCs (C) and stimulated PBMCs (D) among four groups. * p<0.01 vs. CSA or CPS; # p>0.05 vs. CPS.
Mentions: GARP is reportedly a receptor of LAP. We therefore measured the expression of GARP on CD4+ T cells. As GARP is highly expressed on activated T cells, we first stimulated PBMCs with anti-CD3/28 for 24 hours prior to the assay. GARP expression was also measured on CD4+ T cells in freshly isolated PBMCs. Figure 3 shows expression of GARP on CD4+ T cells from each patient in the study. In both stimulated and unstimulated PBMCs, the frequencies of CD4+GARP+ T cells were reduced in ACS patients compared with CSA and CPS patients. In the unstimulated condition, the frequency of circulating CD4+GARP+ T cells (CD4+GARP+ T cells/CD4+ T cells) was reduced in patients with ACS (1.15±0.10%) compared with those with CSA (1.8±0.18%) or CPS (1.91±0.19%) (p<0.005), there was no obvious difference between the CSA and CPS groups (p = 0.68). In the stimulated condition, the frequency of CD4+GARP+ T cells was also reduced in patients with ACS (4.53±0.27%) compared with CSA (6.67±0.42%) and CPS (6.73±0.65%) (p<0.005). No obvious difference was found between the CSA and CPS group (p = 0.94).

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