COSTIMULATION THROUGH CD86 IS INVOLVED IN AIRWAY ANTIGEN-PRESENTING CELL AND T-CELL RESPONSES TO ALLERGEN IN ATOPIC ASTHMATICS

Atopic allergic asthma is characterized by activation of Th2-type T ce lls in the bronchial mucosa, Previous reports have suggested an import ant role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen c hallenge. However, human allergen-specific lines and clones were repor ted to be costimulation independent. We therefore examined CD80 and CD 86 dependence of allergen-induced T cell proliferation and cytokine pr oduction in peripheral blood and bronchoalveolar lavage from atopic as thmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein a nd anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4(+) T cell lines from peripheral blood were examined, proliferation and cyto kine production were found to be independent of CD80 or CD86 costimula tion, However, when cells obtained directly from the airways were exam ined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not ant i-CD80. In addition, bronchoalveolar lavage-adherent cells from asthma tic, but not control subjects showed APC activity to autologous T cell s. This was also inhibited by anti-CD86 but not anti-CD80, Thus allerg en-induced T cell activation and IL-5 production in the airway in asth matic subjects is susceptible to blockade by agents interfering with c ostimulation via CD86, and this may hold therapeutic potential in asth ma.