S. Hodge

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

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.

A marked decrease in L-selectin expression by leucocytes in infants with Bordetella pertussis infection: leucocytosis explained?

Objective:  Infants with Bordetella pertussis infection (whooping cough) have an unexplained lymphocytosis and leucocytosis characterized by an increase in small lymphocytes with convoluted and cleaved nuclei. To characterize these cells immunophenotyping using multiparameter flow cytometry was performed on leucocytes from a group of 11 infants aged 3–6 months with proven pertussis and from uninfected control subjects.