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Role of T Regulatory Cells in the Pathogenesis of Asthma FREE TO VIEW

Yi Yang, MD, PhD; Hong-Liang Zhang, MD; Jiang Wu, MD, PhD
Author and Funding Information

From the Department of Neurology (Drs Yang, Zhang, and Wu), First Hospital of Jilin University, and Department of Neurobiology (Dr Zhang), Care Sciences and Society, Karolinska Institute.

Correspondence to: Hong-Liang Zhang, MD, NVS, Novum, plan 5, Karolinska Institute, SE 141 86, Stockholm, Sweden; e-mail: Hongliang.Zhang@ki.se


Financial/nonfinancial disclosures: The authors have reported to CHEST 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):1282-1283. doi:10.1378/chest.10-1440
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To the Editor:

Smyth and colleagues1 recently reported in CHEST (October 2010) that CD4+FoxP3+ T regulatory cells (Tregs) were increased in BAL of patients with moderate to severe asthma compared with patients with mild asthma and healthy subjects. Their findings are intriguing in that they shed new light on the role of Tregs in the pathogenesis of asthma, but we have some concerns about the interpretation of the results.

Tregs have been revealed to suppress the activity of effector T lymphocytes. However, the hypothesis in their research that the numbers of Tregs would be increased in patients with more severe asthma lacks theoretical support. Although further studies are still needed, data from a series of studies have suggested that there may be an inverse correlation between Treg activity and clinical manifestations of allergic diseases.2 CD4+CD25+ T cells from individuals allergic to grass pollen were less able to suppress proliferation and IL-5 production by CD4CD25 T cells.3 To identify whether clinical disease manifestations of asthma are the cause or the consequence of decreased Treg activity, multiple lines of evidence point to a contributory role of decreased Treg activity in the pathogenesis of asthma. Limited data have supported decreased levels of FoxP3+ Tregs in asthmatic lungs compared with healthy lungs.4 In addition, adoptive transfer of antigen-specific CD4+CD25+ Tregs was found to suppress allergic inflammation and hypersensitivity. Moreover, strategies to boost endogenous Tregs have been proposed as a new focus of research for clinical application of Tregs in allergic diseases such as asthma.

As mentioned by the authors, corticosteroids are known to induce FoxP3 expression and to increase CD4+CD25bright cells.5 In their study, no significant difference was seen in the number of Tregs between mild asthma and healthy control subjects. Taken together, we strongly believe that the increased levels of Tregs in this study primarily arise from the use of corticosteroids.

Another pitfall of the study is that the authors did not use CD4+CD25+FoxP3+ to characterize Tregs, which is a well-established and acknowledged way to differentiate Tregs. Although other subgroups of T cells, including IL-10-secreting T cells, IL-10-secreting natural killer cells, CD8+ Tregs, and IL-17-producing γδT and natural killer cells, also have been shown to have regulatory activities, either CD4+FoxP3+, CD4+CD25+CD127, or CD4+CD25bright could not replace CD4+CD25+FoxP3+ in identifying natural Tregs.

In summary, it is promising to figure out the role of Tregs in the pathogenesis of asthma. Although more studies are needed, Tregs may provide new possibilities for monitoring disease process and developing novel therapeutic strategies for asthma.

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]
 
Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531-562. [CrossRef] [PubMed]
 
Ling EM, Smith T, Nguyen XD, et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004;3639409:608-615. [CrossRef] [PubMed]
 
Luo ZX, Liu EM, Deng B, et al. Role of Foxp3 expression and CD4+CD25+regulatory T cells on the pathogenesis of childhood asthma [in Chinese]. Zhonghua Er Ke Za Zhi. 2006;444:267-271. [PubMed]
 
Hartl D, Koller B, Mehlhorn AT, et al. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol. 2007;1195:1258-1266. [CrossRef] [PubMed]
 

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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]
 
Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531-562. [CrossRef] [PubMed]
 
Ling EM, Smith T, Nguyen XD, et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004;3639409:608-615. [CrossRef] [PubMed]
 
Luo ZX, Liu EM, Deng B, et al. Role of Foxp3 expression and CD4+CD25+regulatory T cells on the pathogenesis of childhood asthma [in Chinese]. Zhonghua Er Ke Za Zhi. 2006;444:267-271. [PubMed]
 
Hartl D, Koller B, Mehlhorn AT, et al. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma. J Allergy Clin Immunol. 2007;1195:1258-1266. [CrossRef] [PubMed]
 
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