title: Down regulation of T cell receptor expression in COPD pulmonary CD8 cells.
abstract: CD8 cells may contribute towards an autoimmune process in COPD. Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction. We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells. Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S). We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence. TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) -2.43, Q = 0.001; LCK: FC -2.25, Q = 0.01). Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells. However, PCR revealed significantly lower gene expression levels of CD247 (FC -1.79, p = 0.04) and LCK (FC -1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells. CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells. This may cause T cell dysfunction.
authors: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester Foundation Trust, Manchester, United Kingdom.
authors: Seamus
authors: S
authors: Grundy
authors: Jonathan
authors: J
authors: Plumb
authors: Simon
authors: S
authors: Lea
authors: Manminder
authors: M
authors: Kaur
authors: David
authors: D
authors: Ray
authors: Dave
authors: D
authors: Singh
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D003710:Demography; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000009:adverse effects / Q000276:immunology
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell
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