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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

CD4+LAP+ Tregs from patients with AMI and UA had reduced capacity to suppress responder T cell proliferation.CD4+LAP+ Tregs and Tresps (CD4+LAP−CD25int/low T cells) from ACS patients (4 patients from the AMI group and 4 from the UA group), and controls (4 patients from CSA group and 4 patients from CPS) were purified by FACS sorting. (A) Reduced suppressive function of CD4+LAP+ Tregs from patients with ACS suggested by suppression assay. (B) Similar proliferative capacity of CD4+LAP−CD25int/low Tresps between ACS group and control (CSA and CPS) group. (C) Crossover experiment with ACS (AMI and UA) and control (CPS and CSA) groups. *p <0.05 vs. Controls.
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pone-0088775-g005: CD4+LAP+ Tregs from patients with AMI and UA had reduced capacity to suppress responder T cell proliferation.CD4+LAP+ Tregs and Tresps (CD4+LAP−CD25int/low T cells) from ACS patients (4 patients from the AMI group and 4 from the UA group), and controls (4 patients from CSA group and 4 patients from CPS) were purified by FACS sorting. (A) Reduced suppressive function of CD4+LAP+ Tregs from patients with ACS suggested by suppression assay. (B) Similar proliferative capacity of CD4+LAP−CD25int/low Tresps between ACS group and control (CSA and CPS) group. (C) Crossover experiment with ACS (AMI and UA) and control (CPS and CSA) groups. *p <0.05 vs. Controls.

Mentions: The ability of CD4+LAP+ Tregs to inhibit the proliferation of CD4+LAP−CD25int/low Tresps was determined using a [3H]-thymidine incorporation assay in co-cultures of Tregs and Tresps in different ratios (1∶1, 1∶2 and 1∶4). Our data demonstrated that CD4+LAP+ Tregs from ACS patients exhibited reduced capacity to suppress the proliferation of Tresps at all ratios compared with those from CSA and CPS groups. We next assessed the proliferation of CD4+LAP−CD25int/low T cells activated by anti-CD3/28; no significant difference was found among the three groups. A crossover experiment between ACS (AMI and UA) patients and control (CPS and CSA) groups also demonstrated that the function of CD4+LAP+ Tregs from ACS patients was impaired (Figure 5).


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)

CD4+LAP+ Tregs from patients with AMI and UA had reduced capacity to suppress responder T cell proliferation.CD4+LAP+ Tregs and Tresps (CD4+LAP−CD25int/low T cells) from ACS patients (4 patients from the AMI group and 4 from the UA group), and controls (4 patients from CSA group and 4 patients from CPS) were purified by FACS sorting. (A) Reduced suppressive function of CD4+LAP+ Tregs from patients with ACS suggested by suppression assay. (B) Similar proliferative capacity of CD4+LAP−CD25int/low Tresps between ACS group and control (CSA and CPS) group. (C) Crossover experiment with ACS (AMI and UA) and control (CPS and CSA) groups. *p <0.05 vs. Controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0088775-g005: CD4+LAP+ Tregs from patients with AMI and UA had reduced capacity to suppress responder T cell proliferation.CD4+LAP+ Tregs and Tresps (CD4+LAP−CD25int/low T cells) from ACS patients (4 patients from the AMI group and 4 from the UA group), and controls (4 patients from CSA group and 4 patients from CPS) were purified by FACS sorting. (A) Reduced suppressive function of CD4+LAP+ Tregs from patients with ACS suggested by suppression assay. (B) Similar proliferative capacity of CD4+LAP−CD25int/low Tresps between ACS group and control (CSA and CPS) group. (C) Crossover experiment with ACS (AMI and UA) and control (CPS and CSA) groups. *p <0.05 vs. Controls.
Mentions: The ability of CD4+LAP+ Tregs to inhibit the proliferation of CD4+LAP−CD25int/low Tresps was determined using a [3H]-thymidine incorporation assay in co-cultures of Tregs and Tresps in different ratios (1∶1, 1∶2 and 1∶4). Our data demonstrated that CD4+LAP+ Tregs from ACS patients exhibited reduced capacity to suppress the proliferation of Tresps at all ratios compared with those from CSA and CPS groups. We next assessed the proliferation of CD4+LAP−CD25int/low T cells activated by anti-CD3/28; no significant difference was found among the three groups. A crossover experiment between ACS (AMI and UA) patients and control (CPS and CSA) groups also demonstrated that the function of CD4+LAP+ Tregs from ACS patients was impaired (Figure 5).

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