Clinical Significance of CD4+CD25highCD127low Regulatory T Cells and Cytokines Detected in COPD Patients with Pulmonary Hypertension_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

MuChuanyong , ChenYanbin , PangXueqin , ChenCheng , ZhuYehan ,  HuangJian'an

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China;

Corresponding author：

HuangJian'an, Email: huang_jian_an@163.com

Keywords：

Pulmonary hypertension; Chronic obstructive pulmonary disease; Regulatory T cells; Cytokines

DOI：

10.7507/1671-6205.2015036

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Objective To investigate the expression of CD4⁺CD25^highCD127^lowTreg (Treg) and related cytokines in peripheral blood of COPD patients with pulmonary hypertension and explore its clinical significance. Methods Peripheral blood lymphocytes and serum were collected from 65 COPD patients with chronic pulmonary hypertension (the CPH group) and 20 COPD patients with normal pulmonary artery pressure (the control group). Flow cytometry was used to detect the Treg/CD4⁺ T cells and calculate its ratio, enzyme-linked immunosorbent assay was used to detect the serum contents of interleukin (IL)-6,IL-10 and tumor necrosis factor α (TNF-α). Results Treg can be detected in the peripheral blood of patients of COPD with or without PH, however, the Treg ratio in the CPH group was significantly lower than that in the control group [(7.41±1.12)% vs. (9.04±2.11)%, P<0.05]. Compared with the control group, the IL-10 level was significantly lower [(4.47±0.88)pg/mL vs. (5.18±0.26)pg/mL], while IL-6and TNF-α contents were significantly higher in the CPH group [(7.49±0.95)pg/mL vs. (6.76±0.35)pg/mL, (28.61±9.16)pg/mL vs. (19.64±4.85)pg/mL, P<0.05]. There was a positive correlation between Treg ratio and serum IL-10 level (r=0.41, P<0.05), and negative correlation between Treg ratio and TNF-α or IL-6 contents (r=0.45 or 0.37,P<0.05). The Treg ratio of the patients with severe pulmonary hypertension was lower than that in the patients with mild pulmonary hypertension [(7.42±1.03)% vs. (10.47±2.55)%,P<0.05). Conclusions Contents of Treg and IL-10 decrease while IL-6 and TNF-α increase in peripheral blood of COPD patients with pulmonary hypertension. It suggests that Treg cells and related cytokines may involve in the pathogenesis and progression of CPH. Treg may becomea potential biological prognosis indicator and treatment target of CPH in the future.

Citation： MuChuanyong, ChenYanbin, PangXueqin, ChenCheng, ZhuYehan, HuangJian'an. Clinical Significance of CD4⁺CD25^highCD127^low Regulatory T Cells and Cytokines Detected in COPD Patients with Pulmonary Hypertension. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(2): 139-142. doi: 10.7507/1671-6205.2015036 Copy

1.	Waxman AB, Zamanian RT. Pulmonary arterial hypertension:new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol,2013,111:1A-16A.
2.	Bossowski A, Moniuszko M, Dabrowska M, et al. Lower proportions of CD4⁺CD25^(high) and CD4⁺Foxp3, but not CD4⁺CD25⁺CD127^(low) Foxp3⁺ T cell levels in children with autoimmune thyroid diseases. Autoimmunity,2013,46:222-230.
3.	Yu N, Li XM, Song WY, et al. CD4⁺CD25⁺CD127^low/- T cells:a more specific Treg population in human peripheral blood. Inflammation,2012,35:1773-1780.
4.	Tamosiuniene R, Tian W, Dhillon G, et al. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res,2011,109:867-879.
5.	Asherson RA, Cervera R. Pulmonary hypertension, antiphospholipid antibodies, and syndromes. Clin Rev Allergy Immunol,2007,32:153-158.
6.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志,2007,30:8-17.
7.	Ganiats TG, Browner DK, Dittrich HC, et al. Comparison of Quality of Well-Being scale and NYHA functional status classification in patients with atrial fibrillation. New York Heart Association. Am Heart J,1998,135:819-824.
8.	Lim SC, Ju JY, Chi SY, et al. Apoptosis of T lymphocytes isolated from peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease. Yonsei Med J,2011,52:581-587.
9.	Crellin NK, Garcia RV, Levings MK. Flow cytometry-based methods for studying signaling in human CD4⁺CD25⁺FOXP3⁺ T regulatory cells. J Immunol Methods,2007,324:92-104.
10.	Graham BB, Chabon J, Kumar R, et al. Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension. Am J Respir Cell Mol Biol,2013,49:951-959.
11.	Caridade M, Graca L, Ribeiro RM. Mechanisms underlying CD4⁺ Treg immune regulation in the adult:from experiments to models. Front Immunol,2013,4:378.
12.	Wang H, Bai J, Zhang J, et al. IL-6 promotes the expression of vascular endothelial growth factor through the p38 signalling pathway in hypertrophied adenoids in children. Int J Pediatr Otorhinolaryngol,2013,77:205-209.
13.	Shao D, Perros F, Caramori G, et al. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension. Biochem Biophys Res Commun,2014,451:8-14.
14.	Feng WJ, Xu XZ, Zhao G, et al. EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. Int J Mol Med,2013,32:685-693.
15.	Zhang Q, Hu LQ, Yin CS, et al. Catechin ameliorates cardiac dysfunction in rats with chronic heart failure by regulating the balance between Th17 and Treg cells. Inflamm Res,2014,63:619-628.
16.	Li N, Bian H, Zhang J, et al. The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. Clin Chim Acta,2010,411:1963-1968.
17.	Ryba-Stanislawowska M, Skrzypkowska M, Mysliwska J, et al. The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediators Inflamm,2013,2013:205284.
18.	Smith KA, Maizels RM. IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo. Eur J Immunol,2014,44:150-161.

1. Waxman AB, Zamanian RT. Pulmonary arterial hypertension:new insights into the optimal role of current and emerging prostacyclin therapies. Am J Cardiol,2013,111:1A-16A.
2. Bossowski A, Moniuszko M, Dabrowska M, et al. Lower proportions of CD4⁺CD25^(high) and CD4⁺Foxp3, but not CD4⁺CD25⁺CD127^(low) Foxp3⁺ T cell levels in children with autoimmune thyroid diseases. Autoimmunity,2013,46:222-230.
3. Yu N, Li XM, Song WY, et al. CD4⁺CD25⁺CD127^low/- T cells:a more specific Treg population in human peripheral blood. Inflammation,2012,35:1773-1780.
4. Tamosiuniene R, Tian W, Dhillon G, et al. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res,2011,109:867-879.
5. Asherson RA, Cervera R. Pulmonary hypertension, antiphospholipid antibodies, and syndromes. Clin Rev Allergy Immunol,2007,32:153-158.
6. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志,2007,30:8-17.
7. Ganiats TG, Browner DK, Dittrich HC, et al. Comparison of Quality of Well-Being scale and NYHA functional status classification in patients with atrial fibrillation. New York Heart Association. Am Heart J,1998,135:819-824.
8. Lim SC, Ju JY, Chi SY, et al. Apoptosis of T lymphocytes isolated from peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease. Yonsei Med J,2011,52:581-587.
9. Crellin NK, Garcia RV, Levings MK. Flow cytometry-based methods for studying signaling in human CD4⁺CD25⁺FOXP3⁺ T regulatory cells. J Immunol Methods,2007,324:92-104.
10. Graham BB, Chabon J, Kumar R, et al. Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension. Am J Respir Cell Mol Biol,2013,49:951-959.
11. Caridade M, Graca L, Ribeiro RM. Mechanisms underlying CD4⁺ Treg immune regulation in the adult:from experiments to models. Front Immunol,2013,4:378.
12. Wang H, Bai J, Zhang J, et al. IL-6 promotes the expression of vascular endothelial growth factor through the p38 signalling pathway in hypertrophied adenoids in children. Int J Pediatr Otorhinolaryngol,2013,77:205-209.
13. Shao D, Perros F, Caramori G, et al. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension. Biochem Biophys Res Commun,2014,451:8-14.
14. Feng WJ, Xu XZ, Zhao G, et al. EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. Int J Mol Med,2013,32:685-693.
15. Zhang Q, Hu LQ, Yin CS, et al. Catechin ameliorates cardiac dysfunction in rats with chronic heart failure by regulating the balance between Th17 and Treg cells. Inflamm Res,2014,63:619-628.
16. Li N, Bian H, Zhang J, et al. The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. Clin Chim Acta,2010,411:1963-1968.
17. Ryba-Stanislawowska M, Skrzypkowska M, Mysliwska J, et al. The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediators Inflamm,2013,2013:205284.
18. Smith KA, Maizels RM. IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo. Eur J Immunol,2014,44:150-161.

Chinese Journal of Respiratory and Critical Care Medicine

Clinical Significance of CD4⁺CD25^highCD127^low Regulatory T Cells and Cytokines Detected in COPD Patients with Pulmonary Hypertension

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