CLINICAL REPORT Expression and Functional Role of Co-stimulatory Molecules in CD40zIL-4-Stimulated B Cells from Atopic and Non-atopic Donors

As immunological dysregulation is a possible key defect in atopic diseases, we have studied the expression and function of costimulatory molecules in atopic dermatitis (AD) patients compared with normal controls. Using ̄ow cytometry, we showed that CD80 and CD86 are expressed at increased levels on human peripheral B cells in both groups after stimulation with anti-CD40 and interleukin 4 (IL-4), but to a signi®cantly higher extent in the AD group. Furthermore, baseline expression of CD80 and CD86 on peripheral B cells was low in normal donors and increased in AD donors. To study the functional role of the costimulatory molecules in CD40zIL-4-stimulated peripheral mononuclear cells from normal and atopic donors, proliferation and IgE production were analysed in the presence of antibodies against the receptors of the costimulatory molecules. In the presence of either anti-CD28 or antiCTLA-4, cell proliferation and IgE synthesis were signi®cantly enhanced in the atopic group in anti-CD40zIL-4-stimulated peripheral mononuclear cells. These ®ndings suggest that interaction of CD80 and CD86 with their receptors CD28 and CTLA-4 selectively promotes cell activation, including proliferation and IgE production in CD40zIL-4-stimulated peripheral blood mononuclear cells from atopic donors. It remains to be elucidated whether these changes are primary, based on the genetic background of atopics, or whether they are induced secondarily in the context of atopic pathology.