Interferon enhancement of HLA-DR antigen expression on epidermal Langerhans cells

Langerhans cells (LCs) are dendritic epidermal cells whose ability to function as accessory/stimulatory cells in initiating the immune response is, like that of macrophages, dependent on the expression of class II major histocompatibility antigens. In normal human skin approximately 50% of LCs identified by cell surface T6 antigenicity also express HLA-DR histocompability determinants. We report here that recombinant DNA-derived human interferon (IFN)-gamma, but not IFN-alpha 2, induces the expression of HLA-DR antigens by the population of human epidermal LCs on which such antigens normally are not detected. IFN-gamma effectively induced HLA-DR on both neonatal and adult epidermal LCs and such induction was blocked by neutralization with a murine monoclonal antibody to IFN-gamma. IFN-gamma induction of LC HLA-DR expression is inhibited by prostaglandin E2 (PGE2) and is mimicked by the presence of fatty acid cyclooxygenase inhibitors, known to reduce PGE2 production. These results suggest that IFN-gamma may play a role in regulating skin-associated immune responses through enhanced expression of HLA-DR antigens on LCs and that such enhancement may be mediated by alterations in arachidonic acid metabolism.