T-Lymphocytes - Chronic Obstructive Pulmonary Disease - page 218

inflammatory cells in the wall of large airways in smokers with chronic
bronchitis and COPD (85). These cytokines play an important role in the
development of asthma, a disease characterized by an increase in airway
reactivity; hence, it is possible that clones of T-cells in smokers with CLE
could express a Th-2 cytokine profile that might induce airway reactivity
in these cases. Furthermore, IL-4 has been shown to have profibrotic effects
by stimulating fibroblasts to proliferate and secrete collagen (86) and this
profibrotic role might be of relevance to the increased remodeling with fibro-
sis in the small airways and in the increased fibrosis in areas of emphysema
found commonly in patients with CLE (84). Further characterization of the
T-cell Th phenotype in the small airways of COPD would be necessary to
confirm these possibilities.
Following the report by Finkelstein et al. (84) proposing a role for the
T-cell in COPD, several authors identified the CD8 þ T-cell as the predomi-
nant lymphocyte in the airways of smokers with COPD. O'Shaughnessy
et al. (87), studying the large airways, and Saetta et al. (88), the small air-
ways, showed that the only significant difference in the inflammatory cell
infiltrate in asymptomatic smokers and smokers with COPD was the
increase in CD8 þ T-cells in patients with COPD. Furthermore, the number
of CD8 þ T-cells was negatively correlated with the degree of airflow
obstruction, as measured by the FEV 1 , again suggesting a possible role
for these cells in the pathogenesis of the disease.
The CD4 þ T-cells are also found, albeit in smaller numbers, in the
airways of smokers with COPD and these cells express activated signal
transducer and activator of transcription 4 (STAT-4), a transcription factor
that is essential for activation and commitment of the Th-1 lineage. Not sur-
prisingly, the number of CD4 þ T-cells expressing activated STAT-4 was
associated with the cells expressing IFN-g, and activated STAT-4 lympho-
cytes correlated with the degree of airflow obstruction (89). These findings
strongly support the idea that COPD is mediated by an active Th-1 immune
reaction in the lung comprising both CD8 þ and CD4 þ T-cells.
Lams et al. (90,91) studying the small and large airways of smokers
reported, as Costabel et al. (92) had years before in BAL, that the
CD8 þ = CD3 þ ratio in the airways increase as the amount smoked
increased, and this ratio decreased after smoking cessation (90). These find-
ings are very suggestive of a direct relationship between smoking and the
recruitment and possible involvement of the CD8 þ T-cell, and in conse-
quence the adaptive immune system, in smokers.
Increased numbers of CD8 þ T-cells can also be found in the adventi-
tia of small pulmonary arteries of smokers when compared with nonsmo-
kers, and this inflammation is greater in smokers with COPD (93,94). The
significance of this finding is unclear, but it has been suggested that it might
be related to the arterial changes seen in smokers.