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

journal contribution
posted on 2011-01-01, 00:00 authored by G Hodge, V Mukaro, P Reynolds, S Hodge
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.

History

Journal

Clinical and experimental immunology

Volume

166

Issue

1

Pagination

94 - 102

Publisher

Wiley

Location

London, England

ISSN

0009-9104

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

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