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Eur Respir J 2007, doi:10.1183/09031936.00010407
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ORIGINAL ARTICLE |
Phenotypic characterization of T-lymphocytes in chronic obstructive pulmonary disease
1 Serveis d'Análisis Clínics; and Ciber Enfermedades Respiratorias, Spain
2 Immunología; and Ciber Enfermedades Respiratorias, Spain
3 Pneumología; Hospital Universitari Son Dureta and Fundació Caubet-CIMERA; and Ciber Enfermedades Respiratorias, Spain
4 Pneumología
* To whom correspondence should be addressed. E-mail: aagusti{at}hsd.es.
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Abstract |
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Tobacco smoking induces an inflammatory response in the lungs of all smokers but, for reasons that are still poorly understood, only a percentage of them develop chronic obstructive pulmonary disease (COPD). Recent evidence indicate that this inflammatory response persists after quitting smoking, suggesting some type of auto-perpetuation mechanism similar to that described in auto-immune disorders. T lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD and several autoimmune processes. A subtype of regulatory CD4+ T cells expressing CD25 (regulatory T cells or Tregs) plays a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity, but their potential role in COPD has not been explored before. This study sought to evaluate maturation (CD45RA/CD45RO) and activation markers (CD28) of T lymphocytes and to explore potential Tregs abnormalities in COPD. To achieve these goals, we used flow cytometry to characterize T lymphocytes obtained from blood and broncho-alveolar lavage fluid (BALF) in 23 patients with moderate COPD, 29 smokers with normal lung function and 7 never smokers. Our main findings were that in BALF: (1) patients with COPD showed higher CD8+CD45RA+ (p<0.001) and lower CD8+CD45RO+ (p<0.005) than smokers with normal lung function; (2) compared to never smokers, smokers with preserved lung function showed a prominent up-regulation of Tregs that was absent in patients with COPD. These observations indicate a final maturation-activation state of CD8+ T lymphocytes in COPD and, for the first time identify a blunted Tregs response to tobacco smoking in these patients, further supporting a potential involvement of the acquired immune response in the pathogenesis of the disease.
Keywords: Flow cytometry, lung inflammation, mucosal homeostasis, tissue repair
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