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)-beta/TGF receptor (TGFR), TNF-alpha/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-alpha/TNFR1, Fas, and TGFR. Monocyte production of TGF-beta 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-beta, TNF-alpha, and Fas in the peripheral blood in COPD.
Hodge
S J
SJ
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia 5001. sandy.hodge@imvs.sa.gov.au
Hodge
G L
GL
Reynolds
P N
PN
Scicchitano
R
R
Holmes
M
M
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D012016:Reference Values; D012907:Smoking; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014797:Vital Capacity
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha