Inflammation in Lung Parenchyma - Chronic Obstructive Pulmonary Disease - page 23

An important effect of CD8 þ T-lymphocytes is the apoptosis of target
cells, and it would be not surprising that apoptosis plays a role in the
destruction of lung tissue in patients with emphysema. Majo et al. (54) have
reported that, in smokers with emphysema, both the degree of apoptosis and
the number of CD8 þ T cells in the alveolar walls increased in parallel with
the amount of cigarette smoke inhaled. Moreover, Kasahara et al. (55)
demonstrated that the destruction of lung tissue in emphysema may involve
accelerated apoptosis of endothelial and epithelial cells through a mechan-
ism dependent on vascular endothelial growth factor (VEGF). It can be
therefore hypothesized that CD8 þ T-lymphocytes may participate in lung
destruction by inducing apoptosis of structural cells.
Although CD8 þ T-lymphocytes may play an important role in the
pathophysiology of COPD, the cytokine profile of these cells and their che-
mokine receptor expression have not been fully investigated. A current para-
digm in immunology is that the nature of an immune response to an
antigenic stimulus is determined largely by the pattern of cytokines pro-
duced by activated T cells (56). Type-1 T cells express cytokines, such as
interferon g (IFN g ), crucial in the activation of macrophages and in the
response to viral and bacterial infections, whereas type-2 T cells express
cytokines, such as interleukin (IL)-4 and -5, involved in Ig-E-mediated
responses and eosinophilia characteristic of allergic diseases. It has recently
been shown that the CD8 þ T cells infiltrating the peripheral airways in
COPD produce IFN g and express CXCR3 (57), a chemokine receptor that
is known to be preferentially expressed on type-1 cells (58). Moreover,
CXCR3 expression is paralleled by a strong epithelial expression of its
ligand CXCL10, suggesting that the CXCR3 = CXCL10 axis may be involved
in the recruitment of type-1 cells in peripheral airways of smokers with
COPD (57).
In smokers peripheral airway inflammation is likely to play a role in
alveolar destruction, particularly in the selective destruction of alveolar
walls directly attached to bronchioles (alveolar attachments). This hypoth-
esis is supported by observation that the destruction of alveolar attachments
in smokers is correlated with the degree of inflammation in peripheral air-
ways (59). It is possible that mediators released by inflammatory cells may
weaken the alveolar tissue and facilitate its rupture, particularly at the point
where the attachments join the airway wall, where the mechanical stress is
maximal. The destruction of alveolar attachments allows the airway wall
to deform, thus narrowing the airway lumen and therefore contributing to
airflow obstruction.
COPD is a progressive disease that in a minority of subjects may wor-
sen toward a very severe stage. Investigating these patients may be of inter-
est because a better characterization of their lung pathology may help to
clarify why, among patients with a similar smoking history, only a minority
develop a severe disease. Furthermore, even if patients with severe COPD