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Lucy J. C. Smyth, PhD; Amanda Eustace, PhD; Umme Kolsum, MSc; John Blaikely, MD; Dave Singh, MD
Author and Funding Information

From the University of Manchester (Drs Smyth, Eustace, Blaikely, Singh, and Ms Kolsum), National Institute for Health Research Translational Research Facility, Manchester Academic Health Science Centre, University Hospital of South Manchester Foundation Trust; and the University of Salford (Dr Smyth), Centre for Parasitology and Disease, School of Environment and Life Sciences, Salford, England.

Correspondence to: Lucy J. C. Smyth, PhD, University of Salford, Centre for Parasitology and Disease, School of Environment and Life Sciences, Salford, M5 4WT, England; e-mail: l.smyth@salford.ac.uk


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Singh has received lectures fees, support for conference attendance, advisory board fees, and research grants from a range of pharmaceutical companies including GlaxoSmithKline, Chiesi Pharmaceuticals, AstraZeneca, CIPLA, Novartis, Forest, MSD, Boehringer, and Allmiral. Drs Smyth, Eustace, and Blaikely and Ms Kolsum have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(5):1283. doi:10.1378/chest.10-1669
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To the Editor:

We thank Yang and colleagues for their interest in our recent article in CHEST (October 2010).1 We found that the number of T regulatory cells (Tregs) was increased in the BAL of patients with moderate to severe asthma. We found evidence of an association, albeit weak (R2 = 0.16, P = .01), between Treg numbers and FEV1, but no association between corticosteroid dose and FEV1. These associations favor the possibility that disease severity has influenced Treg numbers, although our analysis by associations cannot provide a definitive answer as to whether disease severity and/or corticosteroid use are driving the increase in Treg numbers. The concern of Yang et al that our results could be due to corticosteroid use are already discussed extensively in our article.

Yang states that “…there may be an inverse correlation between Treg activity and clinical manifestations of allergic disease.” We could not agree more! Our discussion clearly states that we have studied the numbers of Tregs, but this may not be indicative of functional suppressive ability. It is probable that the Tregs in the lungs of patients with moderate to severe asthma contain a subpopulation of inducible Tregs. These may have a different functional capacity compared with naturally occurring Tregs, and this is clearly an area for further study. The effects of cytokines within the local microenvironment can influence both the induction of Tregs and their functional capacity.2-4 Functional studies using Tregs from the lungs of patients with asthma are technically difficult to perform but will provide clarification of this issue.

Yang et al raise concerns about our method of quantifying Treg numbers. We used three well-cited methods: CD4 + FoxP3 + , CD4 + CD25bright+  and CD4 + CD25 + CD127  . There is no consensus regarding the best method of measuring Treg numbers, so we took a comprehensive approach. Although Yang et al favor CD4 + CD25 + FOXP3 for quantifying Tregs, it should be noted that many scientists agree that CD4 + FoxP3 +  expression is of key importance, as we described previously. We have plotted the data using CD4 + CD25 + FOXP3 (Fig 1), which gives a similar pattern to the analysis using CD4 + FOXP3 (healthy vs moderate/severe, P= .003). Either approach appears valid for identifying Tregs in the airways.

Figure Jump LinkFigure 1. %CD4 + CD25bright FoxP3 +  cells present in healthy patients (n = 6), patients with mild asthma (n = 15), and patients with moderate to severe asthma (n = 13) BAL. **P < .01; horizontal line represents group median.Grahic Jump Location

Smyth LJC, Eustace A, Kolsum U, Blaikely J, Singh D. Increased airway T regulatory cells in asthmatic subjects. Chest. 2010;1384:905-912. [CrossRef] [PubMed]
 
Workman CJ, Szymczak-Workman AL, Collison LW, et al. The development and function of regulatory T cells. Cell Mol Life Sci. 2009;6616:2603-2622. [CrossRef] [PubMed]
 
Ehrenstein MR, Evans JG, Singh A, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy. J Exp Med. 2004;2003:277-285. [CrossRef] [PubMed]
 
van Amelsfort JM, van Roon JA, Noordegraaf M, et al. Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum. 2007;563:732-742. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. %CD4 + CD25bright FoxP3 +  cells present in healthy patients (n = 6), patients with mild asthma (n = 15), and patients with moderate to severe asthma (n = 13) BAL. **P < .01; horizontal line represents group median.Grahic Jump Location

Tables

References

Smyth LJC, Eustace A, Kolsum U, Blaikely J, Singh D. Increased airway T regulatory cells in asthmatic subjects. Chest. 2010;1384:905-912. [CrossRef] [PubMed]
 
Workman CJ, Szymczak-Workman AL, Collison LW, et al. The development and function of regulatory T cells. Cell Mol Life Sci. 2009;6616:2603-2622. [CrossRef] [PubMed]
 
Ehrenstein MR, Evans JG, Singh A, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy. J Exp Med. 2004;2003:277-285. [CrossRef] [PubMed]
 
van Amelsfort JM, van Roon JA, Noordegraaf M, et al. Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum. 2007;563:732-742. [CrossRef] [PubMed]
 
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