The cell surface expression and function of the LFA-1 ligand, intercellular adhesion molecule 1 (ICAM-1), on epidermal keratinocytes (EK) was studied. ICAM-1 expression on the surface of cultured EK was either absent or weak, but was induced by treating EK with rIFN-gamma or TNF for 4-48 h. IFN-gamma and TNF were synergistic. IFN-gamma treatment increased T lymphoblast adhesion from less than 2% to 20-40%, with a concentration dependence similar to that seen for ICAM-1 induction. All of the adhesion to EK was inhibited by LFA-1 and ICAM-1 mAbs, but not by HLA-DR, CD2, or LFA-3 mAbs. There was no difference in the level of T lymphoblast adhesion to IFN-gamma-treated allogeneic or autologous EK. ICAM-1 purified from the HeLa epithelioid cell line and reconstituted into planar membranes also supported efficient adhesion of T lymphoblasts that was blocked by LFA-1 mAb bound to the T lymphoblasts or ICAM-1 mAb bound to the planar membranes. T lymphoblasts adherent to EK or ICAM-1 planar membranes were isolated by panning, and surface markers were analyzed by immunofluorescence flow cytometry. The adherent T cells were a phenotypically skewed subpopulation. They were enriched for CD8+ cells and expressed 1.5-2.5-fold higher LFA-1 and CD2 compared with the unseparated population.
Pemphigus is a severe, blistering disease of the skin and mucous membranes. There is loss of epidermal cohesion manifested clinically by induction of intraepidermal blisters and erosions with mechanical trauma (Nikolski's sign). Biopsies of lesional skin reveal rounding up of epidermal cells with loss of epidermal cell adhesion: this pattern is referred to as acantholysis. Two major types of pemphigus are distinguished clinically and histopathologically. Pemphigus vulgaris exhibits extensive erosions and the vesicles form just above the basal layer of epidermal cells. In contrast, pemphigus foliaceous has very shallow blisters that appear in the more superficial granular layer of the epidermis.In 1964, Beutner and Jordan (1) demonstrated that serum from pemphigus patients contained autoantibodies that bound to an intercellular substance of skin and mucosa. Skin biopsies revealed in vivo deposition of autoantibodies in the epidermis of pemphigus patients (2). Recently, immunoflorescence techniques have shown that pemphigus antibody binds to the surface of mouse epidermal cells (3-5), human epidermal ceils (5, 6), squamous cell carcinoma lines (7,8), and a cervical carcinoma cell line (K. Singer, unpublished results).Michel and Ko (9) reported that incubation of pemphigus antibody with organ cultures of normal human skin resulted in histologic changes identical to those seen in biopsies of skin from pemphigus patients. Schiltz and Michel (10) showed that the IgG fraction of serum was responsible for loss of cellular adhesion in a complementindependent manner.Our laboratory (3) presented evidence that a proteinase was responsible for the * Publication 130 of the Dermatological Research
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