T-Lymphocytes - Chronic Obstructive Pulmonary Disease - page 225

The chemokine and chemokine receptor expression in asthma, a Th-2
T-cell-mediated disease, in sarcoidosis, a Th-1 disease, and in COPD have
recently been described (138). In asthma, virtually all T-cells express IL-4
and CCR4, a receptor for CCR4-specific ligands macrophage-derived
chemokine (MDC) and thymus and activation-regulated chemokine
(TARC), which are strongly upregulated on airway epithelial cells. In sarcoi-
dosis, IFN-g, a Th-1 defining cytokine, was abundantly expressed together
with CXCR3 chemokine receptors in the T-cells. No IL-4, CCR4, and
CCR8 expression was detected in the T-cells of sarcoidosis lesion (138).
These studies indicate that the recruitment of Th-2-activated and Th-1-
activated T-cells into the lung uses very specific chemokines expressed at
the moment of activation, after the T-cell develops a Th-2 or Th-1 commit-
ment in different cytokine microenvironments.
Chemokines and T-cell receptors (TCRs) in smokers have been
reported recently by Saetta et al. (147). All smokers, but mainly those with
COPD, had significant expression of the CXCR3 receptor in the T-cells infil-
trating the lung not found in nonsmokers. Furthermore, IFN-g was coex-
pressed with CXCR3 in patients with COPD, and the interferon-induced
protein-10 (IP-10), the ligand for the CXCR3 receptor, was strongly
expressed in the airways and pulmonary arterioles in smokers with COPD,
but not in smokers and nonsmoker controls. Importantly, the number of
T-cells expressing CXCR3 in the lung, a chemokine receptor restricted to
activated T-cells and NK cells (148,149), correlated inversely with the
FEV 1 = FVC ratio in smokers, suggesting that as the activated T-cells expres-
sing CXCR3, and IFN-g in the lung increase, there is an increase in lung
damage and worsening of the lung function (147).
The T-cells in COPD did not express any of the chemokine receptors
described in asthma (CCR4 and CCR8), indicating that, as with sarcoidosis,
the infiltrating T-cells in COPD are activated, Th-1 committed, utilize Th-1
type of chemokines and receptors to home to the lung (138), and likely use
Th-1 cytokines and functions (cytolysis) as effector tools to damage the lung
tissue (Fig. 6).
These results are a strong indication that the T-cells in COPD which
express phosphorylated STAT-4 and IFN-g are effector cells, activated by
antigenic peptides from the lung in the local lymphoid tissue, and homing
back to the lung, the source of the antigens guided by Th-1 chemokines.
The findings are another indication of an adaptive immune response taking
place in the lung as a response to cigarette-smoke exposure and mediating
tissue injury.
B. Activation of CD8 þ T-Cells
The original role intended for the CD8 þ cytotoxic T-lymphocytes (CTLs)
was the killing of cells infected with intracellular pathogens such as viruses,