Differential role of CD80 and CD86 on alveolar macrophages in the presentation of allergen to T lymphocytes in asthma

In the asthmatic lung the altered expression of costimulatory molecules (CD 80, CD86) by alveolar macrophages contributes to T lymphocyte activation an d expansion. We hypothesized that CD80 and CD86 on alveolar macrophages cou ld differentially support allergic inflammation in adult asthma. Here we st udied 11 subjects with mild allergic asthma and 11 atopic non-asthmatics as controls. Dermatophagoides-specific T cell lines were derived from periphe ral blood from each subject. Bronchoalveolar lavage with evaluation of lung inflammatory cells was performed in all individuals at baseline and 24 h a fter allergen challenge. The expression of CD80 and CD86 costimulatory mole cules by alveolar macrophages was studied and, in parallel, the efficiency of antigen presentation was measured in terms of IL-4 and IL-5 production b y allergen-stimulated autologous T cells. We found that in asthmatic subjec ts (i) the percent of CD80(+), but not CD86(+) alveolar macrophages was inc reased at baseline and did not change following allergen challenge; (ii) CD 86, but not CD80, membrane expression was up-regulated following allergen c hallenge; (iii) both CD80 and CD86 were required to support Th2 cytokine pr oduction by allergen-specific T cells, with a prevalent role of CD86 after allergen challenge. Our data indicate that alveolar macrophages deliver cos timulatory signals via CD80 and CD86, which support the production of Th2 c ytokines by allergen-specific T cells. They also indicate that CD86 in vivo is up-regulated in the 24 h following allergen exposure and that this modu lation is functionally relevant.