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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

Expression of CD25 and FoxP3 on CD8+ T cells before and after adjustment.Representative dot plots show the expression of CD25 and FoxP3 on CD8+ T cells in the peripheral blood obtained from a single subject from each group (A). The original values associated with CD25 and FoxP3 expressed on CD4+T cells in peripheral blood from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21) were comprehensively analyzed (B). To eliminate the mixed effects of inflammatory factors, we calculated the ratios of original values to TNF-α (C) and IL-17 (D). The data are presented as the mean ± SEM, unless otherwise stated. *p<0.05 and **p<0.01. Activation index = CD8+CD25+/CD8+; Treg percentage = CD8+CD25+FoxP3+/CD8+; Treg index = CD8+CD25+FoxP3+/CD8+CD25+; Tc index = CD8+CD25+FoxP3−/CD8+CD25+; Pro-inflammatory index = Tc index/Treg index.
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pone-0111044-g004: Expression of CD25 and FoxP3 on CD8+ T cells before and after adjustment.Representative dot plots show the expression of CD25 and FoxP3 on CD8+ T cells in the peripheral blood obtained from a single subject from each group (A). The original values associated with CD25 and FoxP3 expressed on CD4+T cells in peripheral blood from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21) were comprehensively analyzed (B). To eliminate the mixed effects of inflammatory factors, we calculated the ratios of original values to TNF-α (C) and IL-17 (D). The data are presented as the mean ± SEM, unless otherwise stated. *p<0.05 and **p<0.01. Activation index = CD8+CD25+/CD8+; Treg percentage = CD8+CD25+FoxP3+/CD8+; Treg index = CD8+CD25+FoxP3+/CD8+CD25+; Tc index = CD8+CD25+FoxP3−/CD8+CD25+; Pro-inflammatory index = Tc index/Treg index.

Mentions: In addition, the expression of CD25 and FoxP3 on the CD8+ T cells was determined to evaluate whether the results were consistent with those obtained for the CD4+ T cells (Figure 4). Although the CD8+ T cells had relatively low levels of CD25 and FoxP3, the observed alterations in the subset distribution among the CD8+ T cells were similar to those of the CD4+ T cells. Notably, the CD8+ AI in the patients with AECOPD was enhanced 3.18-fold relative to that of the SCOPD subjects (5.24±0.89% vs 1.65±0.35%, P<0.01) (Figure 4B). However, the CD4+ AI of the AECOPD group was only 1.74 times greater than that of the SCOPD group (17.50±1.32% vs 10.03±1.42%, P<0.01) (Figure 3B). These results indicate that the increased reactivity of CD8+ T cells was involved in acute exacerbations.


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)

Expression of CD25 and FoxP3 on CD8+ T cells before and after adjustment.Representative dot plots show the expression of CD25 and FoxP3 on CD8+ T cells in the peripheral blood obtained from a single subject from each group (A). The original values associated with CD25 and FoxP3 expressed on CD4+T cells in peripheral blood from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21) were comprehensively analyzed (B). To eliminate the mixed effects of inflammatory factors, we calculated the ratios of original values to TNF-α (C) and IL-17 (D). The data are presented as the mean ± SEM, unless otherwise stated. *p<0.05 and **p<0.01. Activation index = CD8+CD25+/CD8+; Treg percentage = CD8+CD25+FoxP3+/CD8+; Treg index = CD8+CD25+FoxP3+/CD8+CD25+; Tc index = CD8+CD25+FoxP3−/CD8+CD25+; Pro-inflammatory index = Tc index/Treg index.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111044-g004: Expression of CD25 and FoxP3 on CD8+ T cells before and after adjustment.Representative dot plots show the expression of CD25 and FoxP3 on CD8+ T cells in the peripheral blood obtained from a single subject from each group (A). The original values associated with CD25 and FoxP3 expressed on CD4+T cells in peripheral blood from healthy nonsmokers (n = 20) and subjects with SCOPD (n = 23) and AECOPD (n = 21) were comprehensively analyzed (B). To eliminate the mixed effects of inflammatory factors, we calculated the ratios of original values to TNF-α (C) and IL-17 (D). The data are presented as the mean ± SEM, unless otherwise stated. *p<0.05 and **p<0.01. Activation index = CD8+CD25+/CD8+; Treg percentage = CD8+CD25+FoxP3+/CD8+; Treg index = CD8+CD25+FoxP3+/CD8+CD25+; Tc index = CD8+CD25+FoxP3−/CD8+CD25+; Pro-inflammatory index = Tc index/Treg index.
Mentions: In addition, the expression of CD25 and FoxP3 on the CD8+ T cells was determined to evaluate whether the results were consistent with those obtained for the CD4+ T cells (Figure 4). Although the CD8+ T cells had relatively low levels of CD25 and FoxP3, the observed alterations in the subset distribution among the CD8+ T cells were similar to those of the CD4+ T cells. Notably, the CD8+ AI in the patients with AECOPD was enhanced 3.18-fold relative to that of the SCOPD subjects (5.24±0.89% vs 1.65±0.35%, P<0.01) (Figure 4B). However, the CD4+ AI of the AECOPD group was only 1.74 times greater than that of the SCOPD group (17.50±1.32% vs 10.03±1.42%, P<0.01) (Figure 3B). These results indicate that the increased reactivity of CD8+ T cells was involved in acute exacerbations.

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