© 2007 American Thoracic Society
Dendritic Cell Maturity and Obstructive Airway DiseaseTo the Editor:We read with interest the article by Demedts and colleagues, who evaluated, by immunohistochemistry, the increased infiltration of small airways by dendritic cells (DCs) in chronic obstructive pulmonary disease (COPD) (1). In asthma, we have reported a decrease in the number of mature DCs (mDCs) in endobronchial biopsies of current smokers by comparison with never-smokers (2). Also, we have unpublished data showing that the bronchial mucosa of patients with COPD has fewer mDCs than normal healthy nonsmoker controls and that current smokers have significantly fewer sputum mDCs than ex-smokers with or without COPD. What might be a possible explanation for these apparent differences? The identification of the distinct immunophenotypes of DCs depends on the method applied. Fluorescence activated cell sorter (FACS) analysis of cells isolated from lung digests, bronchoalveolar lavage fluid, or sputum allows identification of Langerhans' cells (LCs), myeloid DCs types 1 and 2, and plasmacytoid DCs, and distinguishes between mDCs and immature DCs (iDCs). In tissue, immunohistochemistry can identify LCs (CD1a+, Langerin+) and mDCs (CD83+), but other DC phenotypes are not detected reliably in paraffin wax–embedded material. Demedts and colleagues applied an antibody directed against Langerin and thus provide interesting data on the increased numbers of LCs, an important subset of DCs, but their article does not address changes in the numbers of mDCs. Moreover, the LCs that stained positively for Langerin were most likely immature, as Langerin expression is down-regulated upon maturation. Interestingly, cigarette smoke has been shown in vitro to suppress DC maturation (3), and incubation of LPS-matured DCs with sputum from patients with COPD decreases expression of costimulatory molecules on mDCs and inhibits DC maturation (4). Thus, DC maturation is likely attenuated in healthy smokers and in smokers with obstructive airway disease. The reciprocal of this may be an increase in the numbers of iDCs reported by Demedts and coworkers (1). Finally, decreased DC maturation may shift the CD4+/CD8+ T-cell ratio in the lungs toward CD8+ cells, as the time required for DCs to launch the proliferative program for CD8+ is less than that required for CD4+ cells (5). As the proliferative capacity of CD8+ cells is greater than that of CD4+ cells, the latter are more susceptible to the effects of reduced DC maturation (6). The hypothesis that cigarette smoke–induced reduction of DC maturation is associated with development of the "abnormal" or exaggerated inflammation associated with smokers and COPD, or to resistance of asthmatic smokers to steroid therapy, should be tested.
Imperial College London and Royal Brompton Hospital, London, United Kingdom FOOTNOTES Conflict of Interest Statement: M.T. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.K.J. has been reimbursed by GlaxoSmithKline (GSK), AstraZeneca, and Merck, Sharp & Dohme (Merck) for attending several conferences and has participated as a paid speaker in scientific meetings or courses organized and financed by GSK, AstraZeneca, Merck, and Boehringer Ingelheim; he has served as a consultant to GSK and Novartis, and in the last 3 years has held research grants from GSK, Merck, and AstraZeneca. REFERENCES
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