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Treg/IL-17 ratio and Treg differentiation in patients with COPD.

Jin Y, Wan Y, Chen G, Chen L, Zhang MQ, Deng L, Zhang JC, Xiong XZ, Xin JB - PLoS ONE (2014)

Bottom Line: Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups.All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation. An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes. T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses. This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).

Methods: Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study. In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls. The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies. Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.

Results: Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment. There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups. Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient. Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.

Conclusions: These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating. Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation. All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.

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Related in: MedlinePlus

Flow cytometric analysis of CD4+ and CD8+ T cells in peripheral blood.Lymphocytes were gated on forward scatter height (FSC-H) versus side scatter height (SSC-H) plots, and representative dot plots gated on lymphocytes show CD3+CD4+ T cells (A) and CD3+CD8+ T cells (C) in the peripheral blood obtained from a single subject from each group. The collective analyses show the expression of CD4 (B) and CD8 (D) on CD3+ T cells from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21). The data are presented as the mean ± SEM, unless otherwise stated.
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pone-0111044-g002: Flow cytometric analysis of CD4+ and CD8+ T cells in peripheral blood.Lymphocytes were gated on forward scatter height (FSC-H) versus side scatter height (SSC-H) plots, and representative dot plots gated on lymphocytes show CD3+CD4+ T cells (A) and CD3+CD8+ T cells (C) in the peripheral blood obtained from a single subject from each group. The collective analyses show the expression of CD4 (B) and CD8 (D) on CD3+ T cells from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21). The data are presented as the mean ± SEM, unless otherwise stated.

Mentions: To determine the differences between the T-lymphocyte subsets between the COPD patients and the healthy nonsmokers, the authors next performed flow cytometry on mononuclear cells from peripheral blood (Figure 2). To our surprise, no significant differences were observed in the ratio of Th (CD4+) to T(CD3+) cells among the three groups (Figure 2A and B). Similarly, there were no significant differences among the groups for the ratio of Tc (CD8+) to T(CD3+) cells (Figure 2C and D).


Treg/IL-17 ratio and Treg differentiation in patients with COPD.

Jin Y, Wan Y, Chen G, Chen L, Zhang MQ, Deng L, Zhang JC, Xiong XZ, Xin JB - PLoS ONE (2014)

Flow cytometric analysis of CD4+ and CD8+ T cells in peripheral blood.Lymphocytes were gated on forward scatter height (FSC-H) versus side scatter height (SSC-H) plots, and representative dot plots gated on lymphocytes show CD3+CD4+ T cells (A) and CD3+CD8+ T cells (C) in the peripheral blood obtained from a single subject from each group. The collective analyses show the expression of CD4 (B) and CD8 (D) on CD3+ T cells from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21). The data are presented as the mean ± SEM, unless otherwise stated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199736&req=5

pone-0111044-g002: Flow cytometric analysis of CD4+ and CD8+ T cells in peripheral blood.Lymphocytes were gated on forward scatter height (FSC-H) versus side scatter height (SSC-H) plots, and representative dot plots gated on lymphocytes show CD3+CD4+ T cells (A) and CD3+CD8+ T cells (C) in the peripheral blood obtained from a single subject from each group. The collective analyses show the expression of CD4 (B) and CD8 (D) on CD3+ T cells from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21). The data are presented as the mean ± SEM, unless otherwise stated.
Mentions: To determine the differences between the T-lymphocyte subsets between the COPD patients and the healthy nonsmokers, the authors next performed flow cytometry on mononuclear cells from peripheral blood (Figure 2). To our surprise, no significant differences were observed in the ratio of Th (CD4+) to T(CD3+) cells among the three groups (Figure 2A and B). Similarly, there were no significant differences among the groups for the ratio of Tc (CD8+) to T(CD3+) cells (Figure 2C and D).

Bottom Line: Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups.All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation. An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes. T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses. This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).

Methods: Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study. In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls. The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies. Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of "inflammation adjustment" and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.

Results: Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment. There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups. Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient. Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.

Conclusions: These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating. Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation. All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.

Show MeSH
Related in: MedlinePlus