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Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease

Hodge, G., Mukaro, V., Reynolds, P.N. and Hodge, S. 2011, Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease, Clinical and experimental immunology, vol. 166, no. 1, pp. 94-102, doi: 10.1111/j.1365-2249.2011.04455.x.

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Title Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease
Formatted title Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease
Author(s) Hodge, G.
Mukaro, V.
Reynolds, P.N.
Hodge, S.
Journal name Clinical and experimental immunology
Volume number 166
Issue number 1
Start page 94
End page 102
Total pages 9
Publisher Wiley
Place of publication London, England
Publication date 2011
ISSN 0009-9104
Keyword(s) CD8/CD28null T cells
COPD
co-stimulatory molecules
granzyme
smoking mouse model
Summary Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease; it is a leading cause of death and existing treatments have no proven disease-modifying effect. The mechanisms underlying this resistance are largely unknown, but suggest the presence of some self-maintaining pathogenic process, possibly initiated by cigarette smoking, that prevents the normal resolution of inflammation. We have previously reported increased production of proinflammatory cytokines and granzyme b by CD8+ T cells in COPD; costimulatory receptor/ligand interactions required include CD80:86/CD28, B7-1/CTLA4, 4-1BB/1BBL and OX40/OX40L. We hypothesized that a dysregulated expression/function of these molecules may play a role in inflammatory/autoimmune components of COPD. We analysed T cell co-stimulatory molecules in blood from 34 controls, 15 smokers and 48 COPD subjects. We assessed the potential functional relevance of CD8/CD28null cells in COPD by measuring their production of proinflammatory cytokines, co-stimulatory molecules, granzyme and perforin. A smoke-exposed murine model was applied to investigate the relative expression of CD8/CD28null T cells in blood, lung tissue and airway. CD8/CD28null cells were increased in both current- and ex-smoker COPD groups; these cells expressed significantly more interferon (IFN)-γ, OX40, 4-1BB, CTLA4, granzyme and perforin when stimulated than CD8/CD28+ T cells. There were no changes in CD4/CD28null T cells. In mice exposed to cigarette smoke for 12 weeks, CD8/CD28null T cells were significantly increased in the airway with a trend for an increase in lung tissue and blood. Increased production of proinflammatory cytokines and expression of alternative co-stimulatory molecules by CD8/CD28null T cells may play a role in inflammatory or autoimmune responses in COPD and identify therapeutic targets.
Language eng
DOI 10.1111/j.1365-2249.2011.04455.x
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30053416

Document type: Journal Article
Collection: School of Medicine
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