Allergens and irritants transcriptionally upregulate CD80 gene expression in human keratinocytes

The human CD80 costimulatory molecule is an important signal between profes sional antigen-presenting cells and T helper cells. The immunobiology of CD 80 expression by keratinocytes, especially during allergic and irritant con tact dermatitis, however, is less well understood. CD80 cell surface expres sion and gene transcription by keratinocytes was increased when keratinocyt es were exposed to certain allergens (chemicals that induce inflammation vi a hapten-specific T cells) and irritants (chemicals that are toxic to epide rmal cells). Therefore, the human CD80 promoter was cloned and luciferase r eporter constructs containing various promoter fragments were engineered. P romoter mapping of these CD80 constructs in transiently transfected keratin ocytes showed that a construct containing the proximal 231 bp immediately u pstream of the transcription start site of the CD80 promoter was most activ e in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compa red with untreated keratinocytes. This pattern of promoter fragment activit y in keratinocytes is identical to that found in professional antigen-prese nting cells. This is the first demonstration that the CD80 promoter is acti ve in keratinocytes and that this activity is further increased in keratino cytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby f acilitating interactions with epidermotropic T helper cells via the CD80-CD 28 or CTLA-4 pathways.