Intercellular adhesion molecule (ICAM)‐3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM‐1 and ICAM‐2. All three ICAMS are cognate for the counter‐receptor lymphocyte function associated antigen‐1 (LFA‐L CD11a/CD18). Unlike ICAM‐1 and ICAM‐2. ICAM‐3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM‐3 in normal skin (n= 5), as well as its expression in psoriasis (n= 4). atopic eczema (n= 4), allergic (rhus) contact dermatitis (n=3). and cutaneous T‐cell lymphoma (CTCL. n=2).

Five‐micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM‐3 and A well characterized immunoperoxidase technique. In normal skin. ICAM‐3 was expressed by all cutaneous leucocytes hut most striking was the strong expression of ICAM‐3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double‐labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL. ICAM‐3 was co‐expressed on all CD1a⁺ cells, although, in psoriasis, the intensity of ICAM‐3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM‐3 expression on Langerhans cells was functionally important in antigen presentation. CD4⁺ T cells were prepared from peripheral blood and 10⁵ CD4⁺ T cells combined with 10⁵ epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T‐cell donor. Addition of 50 μg anti‐ICAM‐3 to the co‐culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti‐LFA‐1.

These data indicate that ICAM‐3 is constitutively expressed by Langerhans cells and is a major ligand for LFA‐1 on CD4⁺ T cells during their response to Langerhans cells. Because fresh Langerhans ceils constitutively express little ICAM‐1. whereas ICAM‐3 is constitutively expressed at high levels, it would appear that 1CAM‐3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.