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Eur Respir J 2001; 17:946-953
Copyright ©ERS Journals Ltd 2001

Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema

J. Majo1, H. Ghezzo2 and M.G. Cosio3

1 Dept d'Anatomia Patologica, Hospitals Universitaris Vall d'Hebron, Barcelona, Spain, 2 Meakins Christie Laboratories, Montreal, Quebec, Canada and 3 MUHC Respiratory Division, Royal Victoria Hospital & Meakins Christie Laboratories, Montreal, Quebec, Canada

CORRESPONDENCE: M.G. Cosio, McGill University, Respiratory Division, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec, Canada, H3A 1A1. Fax: 1 5148431695

Keywords: apoptosis, CD8+, chronic obstructive pulmonary disease, emphysema, T-cells, T-lymphocytes

Received: July 3, 2000
Accepted December 12, 2000

Supported in part by the Costello J.T. Memorial Fund and the Medical Research Council of Canada Center of Excellence "Inspiraplex". J. Majo was funded by the Barcelona-Quebec Exchange Fellowship and the Canadian Lung Association Fellowship.

Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers.

Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, {gamma}{delta} T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells·mm alveolar wall–1, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery.

Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. {gamma}{delta} cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers·mm alveolar wall–1 showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr–1 (R2=0.345; p<0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p<0.009).

It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.




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