Intercellular Adhesion Molecule Expression in the Evolving Human Cutaneous Delayed Hypersensitivity Reaction

Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. lmmunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48h. ICAM-1 expression was documented focally within the lower epidermis at 48h and diffusely within the lower and upper epidermal layers at 96h. ICAM-1 expression by kentinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity.