Increased production of TGF-beta and apoptosis of T lymphocytes isolated from peripheral blood in COPD

Chronic obstructive pulmonary disease (COPD) is associated with inflammation of airway epithelium, including an increase in the number of intraepithelial T cells. Increased apoptosis of these T cells has been reported in the airways in COPD, and although this process is critical for clearing excess activated T cells, excessive rates of apoptosis may result in unbalanced cellular homeostasis, defective clearance of apoptotic material by monocytes/macrophages, secondary necrosis, and prolongation of the inflammatory response. Lymphocytes are known to traffic between the airway and the peripheral circulation, thus we hypothesized that in COPD, circulating T cells may show an increased propensity to undergo apoptosis. We analyzed phytohemagglutinin (PHA)-stimulated peripheral blood T cells from COPD patients and controls for apoptosis using flow cytometry and staining with annexin V and 7-aminoactinomycin D. As several pathways are involved in induction of apoptosis of T cells, including transforming growth factor (TGF)-β/TGF receptor (TGFR), TNF-α/TNFR1, and Fas/Fas ligand, these mediators were also investigated in peripheral blood samples from these subject groups. Significantly increased apoptosis of PHA-stimulated T cells was observed in COPD (annexin positive 75.0 ± 14.7% SD vs. control 50.2 ± 21.8% SD, P = 0.006), along with upregulation of TNF-α/TNFR1, Fas, and TGFR. Monocyte production of TGF-β was also increased. In conclusion we have demonstrated the novel finding of increased apoptosis of stimulated T cells in COPD and have also shown that the increased T-cell death may be associated with upregulation of apoptotic pathways, TGF-β, TNF-α, and Fas in the peripheral blood in COPD.S. J. Hodge , G. L. Hodge , P. N. Reynolds , R. Scicchitano , M. Holme