Functional Intercellular Adhesion Molecule-3 Is Expressed by Freshly Isolated Epidermal Langerhans Cells and Is Not Regulated During Culture

Abstract

Activation of T lymphocytes by antigen-presenting cells requires the interaction of major histocompatibility complex/antigen complexes with the T-cell receptor as well as the binding of co-stimulatory molecules to receptors on T cells. Freshly isolated epidermal Langerhans cells (LC) do not display a significant number of co-stimulatory molecules. After short-term culture, LC express and then upregulate intercellular adhesion molecule-1 (ICAM-1) (CD54), leukocyte function-associated antigen (LFA)-3 (CD58), and B7-1 (CD80) accessory molecules and exhibit an enhanced antigen-presenting function. The present study examined the presence on human LC of the LFA-1 ligands ICAM-2 (CD102) and ICAM-3 (CD50) and their functional role in the activation of allogeneic T cells. Immunohistochemistry of skin sections and flow-cytometry analysis of freshly procured epidermal cell suspensions showed that LC (CD1a+ or HLA-DR+) expressed ICAM-3 but not ICAM-2. After 48-72-h culture in the presence of granulocyte/macrophage colony-stimulating factor, LC did not stain for ICAM-2 but expressed ICAM-3 at the same level as fresh cells. Incubation of both freshly isolated and cultured LC with monoclonal antibodies directed against ICAM-3 reduced T-cell proliferation (25-75% inhibition) in the primary allogeneic mixed leukocyte reaction assay; incubation of cultured LC with anti-ICAM-1 and anti-ICAM-3 synergistically reduced T-cell response. The results indicate that ICAM-3 is constitutively expressed and represents an important costimulatory molecule on freshly isolated LC but, in contrast to other accessory molecules, is not subjected to regulation during LC culture.