Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/66896
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Type: Journal article
Title: Role of increased CD8/CD28(null) T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease
Author: Hodge, G.
Mukaro, V.
Reynolds, P.
Hodge, S.
Citation: Clinical and Experimental Immunology, 2011; 166(1):94-102
Publisher: Blackwell Publishing Ltd
Issue Date: 2011
ISSN: 0009-9104
1365-2249
Statement of
Responsibility: 
G. Hodge, V. Mukaro, P. N. Reynolds and S. Hodge
Abstract: 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/CD28(null) 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/CD28(null) T cells in blood, lung tissue and airway. CD8/CD28(null) 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/CD28(null) T cells. In mice exposed to cigarette smoke for 12 weeks, CD8/CD28(null) 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/CD28(null) T cells may play a role in inflammatory or autoimmune responses in COPD and identify therapeutic targets.
Keywords: CD8/CD28null T cells
COPD
co-stimulatory molecules
granzyme
smoking mouse model
Rights: © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology
DOI: 10.1111/j.1365-2249.2011.04455.x
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