Mechanisms of allergy and clinical immunologyIncreased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma
Section snippets
Human subjects
The study subjects were recruited from the outpatient clinics of National Jewish Health. The study protocol for bronchoscopy and BAL was approved by the institutional review board. Informed consent was obtained from study subjects. Patients were allowed to continue their routine medication.
Processing of BAL fluid cells and flow cytometry
Bronchoscopy and BAL were performed, as described previously.23 BAL fluid was processed immediately. Cells were isolated by means of centrifugation. Supernatant fluid was placed into aliquots in small samples
Detection of single TH2 and TH17 cells and dual TH2/TH17 cells in BAL fluid from asthmatic patients
We studied BAL cells from 52 asthmatic patients and 25 disease control subjects. Most of the patients were referred to National Jewish Health for diagnosis and management of refractory asthma. Others were referred for routine asthma care. We use the term refractory in this article to indicate uncontrolled asthma, which could be moderate or severe, as determined based on the Expert Panel Report 3 criteria. The clinical characteristics of the study subjects are shown in Table I. Bronchoscopy and
Discussion
The presence of allergic sensitivity (skin test result positivity or IgE-specific antibody in serum) can be detected in a vast majority, but not all, asthmatic patients.34 In addition to IgE, mild-to-moderate eosinophilia is a characteristic feature of asthma. Interestingly, some nonallergic asthmatic patients also have blood eosinophilia. Both IgE antibody and eosinophilia are driven by a TH2-type immune response. Thus the presence of TH2 cells in lung tissue and BAL fluid is anticipated and
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Supported by National Institutes of Health (NIH) grants RO1 AI091614 and N01 HHSN272200700048C to R.A. M.M.G. is supported by career development grants from CCTSI (NIH/NCATS Colorado CTSI KL2 TR000156) and Children's Environmental Center grant from the National Institute of Environmental Health Sciences (NIEHS PO1 ES-018181/EPA GAD 834515010).
Disclosure of potential conflict of interest: J. Good has provided chart reviews for Lincare–Wheeler Trigg O'Donnell LLP, Faraci Wolanske LLC, and Pryor Johnson Carney Karr Nixon PC; is employed by National Jewish Health; has received research support from MedImmune; has received payment for lectures from Merck and Genentech; has received payment for development of educational presentations from QuantiaMD; and has received travel expenses from the Aspen Lung Conference. M. M. Gorska has received research support from the Denver Children's Environmental Health Center Faculty Development Investigator Award, the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences Colorado CTSI KL2 TR000156 Award, and the Sheldon C. Siegel–Asthma and Allergy Foundation of America Investigator Grant Award. R. J. Martin has received honoraria for consultancy and travel from Teva Pharmaceuticals and Boehringer Ingelheim; has received research support from MedImmune; and has received royalties from UpToDate. R. Alam has received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.