Increased expression of plasma and cell surface co-stimulatory molecules CTLA-4, CD28 and CD86 in adult patients with allergic asthma


Professor C. W. K. Lam, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.


The co-stimulatory interactions of the B7 family molecules CD80 and CD86 on antigen-presenting cells, together with their T cell counter receptors CD28 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), modulate T lymphocyte-mediated immune responses in a reciprocal manner. To investigate whether there is altered expression and the clinical significance of soluble co-stimulatory molecules in asthmatic patients, plasma concentrations of sCTLA-4, sCD28, sCD80 and sCD86 in 51 adult allergic asthmatic adults with or without steroid treatment, and 35 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Cell surface expression of CTLA-4 and CD28 on peripheral blood mononuclear cells (PBMC) were analysed by flow cytometry. Results showed that the plasma sCTLA-4 concentration was significantly higher in all asthmatic patients while sCD28 and sCD86 concentrations were significantly higher in steroid and non-steroid treated asthmatic patients, respectively, compared with control subjects (all P < 0·01). Significantly increased cell surface expression of CD28 but not CTLA-4 on PBMC was found in asthmatic patients compared with controls (P < 0·05). The plasma concentration and cell surface expression of CTLA-4 were found to exhibit positive and significant correlations with those of CD28 (both P < 0·05). Serum total IgE concentration correlated positively and significantly with sCTLA-4 and sCD28 concentrations in allergic asthmatic patients (both P < 0·05). The increased expression of these soluble co-stimulatory molecules may reflect the dysregulation of T cell activation, thereby contributing to the immunopathogenesis of allergic asthma.