The effect of in vivo interferon-gamma on the distribution of LFA-1 and ICAM-1 in normal human skin

Abstract

Lymphocyte function associated antigen 1 (LFA-1) and its ligand intercellular adhesion molecule 1 (ICAM-1) are cell surface adhesion molecules important in many lymphocyte-mediated responses. Recent in vitro studies have demon-strated that the cytokine interferon-gamma (IFN-γ) can in-duce ICAM-1 expression by keratinocytes, and that lymphocytes adhere to IFN-γ treated keratinocytes. In view of the importance of keratinocyte/lymphocyte interactions in the pathogenesis of cutaneous disease, we have examined the effects of in vivo IFN-γ on cutaneous expression of LFA-1 and ICAM-1. Fourteen volunteers received intradermal IFN-γ (dose: 1 or 10μg) daily for 3 d. Biopsy was obtained on day 6. Cryostat sections were stained by the peroxidase anti-peroxidase technique employing murine monoclonal anti-bodies to CD11, CD18, and ICAM-1. IFN-γ intensified ICAM-1 expression by dermal endothelial cells and induced keratinocyte expression of ICAM-1. Furthermore, after administration of 10 μg of IFN-γ LFA-1 positive (LFA + ve) lymphocytes were observed along the basement membrane zone closely related to ICAM-1 + ve basal keratinocytes and also surrounding dermal endothelium. Exposure to IFN-γ induced expression of both CD11a and CD18 antigens on epidermal Langerhans cells. These studies suggest that the distribution of adherence molecules expression within cuta-neous tissue in vivo is modulated by IFN-γ, and that these alterations may be important in interactions involving cuta-neous immunocompetent cells. © 1989.