Previously, it had been shown that T-lymphocytes are the predominant inflam
matory cells found in the alveolar wall of smokers and their numbers correl
ated with the extent of emphysema. However, the phenotype of these cells wa
s not defined. The aim of this study was to describe the different T-cell p
henotypes and investigate the possible presence of apoptosis in the lung pa
renchyma 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 histologica
l and immunocytochemical examination. Slides were stained for CD3+, CD4+, C
D8+, gamma delta T-cells, CD56 natural killers ((INK) cells), and elastase
(neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling te
chniques were used to detect Fas expression and apoptosis. Positive stainin
g cells were expressed as cells-mm alveolar wall(-1), percentage of total c
ells, and Fas/APO and apoptosis index. Emphysema was identified macroscopic
ally, microscopically and reported as present or absent. All subjects had p
ulmonary 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 cel
ls were increased in all smokers and no increased numbers of NK cells was f
ound. The T-cell numbers-min alveolar wall(-1) showed a bilinear relationsh
ip with the amount smoked increasing at an 2 inflection point of 30 packs y
r(-1) (R-2 = 0.345; p < 0.01). Apoptosis in smokers showed a bilinear relat
ionship with the amount smoked increasing sharply in smokers with emphysema
(R-2 = 0.3613; p < 0.009).
It is concluded that the pathogenesis of emphysema might be mediated by T-l
ymphocytes. mainly CD8+ cytolytic T-cells, and that apoptosis might be one
of the mechanisms of lung destruction leading to the development of emphyse
ma. 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 cig
arette smoking.