EFFECTS OF CD40 LIGATION ON HUMAN KERATINOCYTE ACCESSORY FUNCTION

CD40/CD40 ligand interactions are known to play a key role in the deve lopment of immune reactions, especially by enhancing the costimulatory function of professional antigen-presenting cells (APC). Little is kn own, however, about the role this receptor plays on occasional APC, i. e. cells that are induced to express MHC class II molecules following an inflammatory process. In this study, we used CD40 ligand-transfecte d cells to analyze the effect of CD40 ligation on the phenotype, as we ll as accessory function, of human keratinocytes. We found that CD40 l igation enhanced ICAM-1 expression and did not upregulate HLA-DR, CD80 or CD86 expression on IFN-gamma-treated keratinocytes. CD40 triggerin g was not sufficient to generate primary allogeneic T-cell responses e ven in the presence of anti-CD28 monoclonal antibody (mAb). Moreover, CD40 ligation, in the presence or not of IFN-gamma, did not alter the accessory function of keratinocytes in PHA- or superantigen-induced T- cell activation. The lack of effect on the T-cell response was confirm ed in blocking experiments using anti-CD40 mAbs. Collectively, these r esults suggest that CD40-CD40 ligand interactions on nonprofessional A PC may amplify the inflammatory reaction without providing a mitogenic signal to the T cells.