Asthma and lower airway disease
Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease

https://doi.org/10.1016/j.jaci.2012.09.030Get rights and content

Background

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined. Nontypeable Haemophilus influenzae (NTHi) is the dominant bacterium isolated from the lungs of patients with COPD. Objective: We sought to measure the response of lung tissue T cells to stimulation with NTHi.

Methods

We obtained lung tissue from 69 subjects having lobectomies for lung cancer. Of the group, 39 subjects had COPD, and 30 without COPD were classified as control subjects. The lung tissue was dispersed into single-cell suspensions and stimulated with live NTHi. Cells were labeled with antibodies for 5 important inflammatory mediators in patients with COPD and analyzed by using flow cytometry.

Results

NTHi produced strong activation of both TH cells and cytotoxic T cells in the COPD cohort. The COPD cohort had significantly higher levels of cells producing TNF-α, IL-13, and IL-17 in both T-cell subsets. When control subjects were divided into those with and without a significant smoking history and compared with patients with COPD, there was a progressive increase in the numbers of T cells producing cytokines from nonsmoking control subjects to smoking control subjects to patients with COPD.

Conclusion

NTHi activates lung T cells in patients with COPD. This proinflammatory profibrotic response might be a key cause of inflammation in patients with COPD and has implications for treatment.

Section snippets

Study subjects

We recruited adults with COPD who were undergoing lobectomies for the treatment of lung cancer at Monash Medical Centre/Southern Health or Cabrini Hospital, Melbourne, Australia. Subjects had COPD defined by using standard criteria (FEV1/forced vital capacity ratio <0.7 and not fully reversible).21 Control subjects did not have airflow obstruction on lung function testing. The study was approved by the Monash Medical Centre/Southern Health and Cabrini Hospital research ethics committee, and all

Characteristics of subjects

Sixty-nine subjects had specimens obtained that were analyzed for their T-cell responses to stimulation with NTHi. Patients' characteristics are listed in Table I (and see Table E1 in this article's Online Repository at www.jacionline.org).

T-cell response to SEB

Subjects in the control and COPD groups demonstrated clear T-cell mediator/cytokine production to stimulation with SEB, thus demonstrating the validity of our method to measure lymphocyte responses. There were no significant differences in the responses

Discussion

This study shows that NTHi is an important pathogen that activates lung T cells in patients with COPD. This activation led to the production of cytokines previously been shown to be important in the pathogenesis of COPD.

Airway inflammation persists in patients with COPD despite the cessation of smoking. Hogg et al7 described the presence of large numbers of lymphocytes in the small airways, and these cells are thought to have a key role in driving the inflammatory process.24 Sullivan et al8

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    Supported by a Strategic Grant, Faculty of Medicine, Nursing and Health Sciences, Monash University (to P.T.K.).

    Disclosure of potential conflict of interest: P. W. Holmes has received one or more payments for presentations to general practitioners and has received one or more payments for travel from Novartis. The rest of the authors declare that they have no relevant conflicts of interest.

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