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

¹Department of Thoracic Medicine, Royal Adelaide Hospital; ²Department of Medicine, University of Adelaide, Adelaide 5001; and ³Haematology Department, Women's and Children's Hospital, North Adelaide 5006, South Australia, Australia

Submitted 16 December 2002 ; accepted in final form 8 March 2003

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)-/TGF receptor (TGFR), TNF-/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-/TNFR1, Fas, and TGFR. Monocyte production of TGF- 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-, TNF-, and Fas in the peripheral blood in COPD.

apoptosis; blood; cytokine; chronic obstructive pulmonary disease; transforming growth factor-

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