Adhesion molecules CD11a, CD18, and ICAM-1 on human epidermal Langerhans cells serve a functional role in the activation of alloreactive T cells.
Binding of antigen-presenting cells (APC) to T cells via adhesion molecules is thought to deliver accessory signals that are required for efficient T-cell activation. To determine whether Langerhans cells (LC) express relevant adhesion molecules on their surfaces, we employed two-color immunofluorescence. Human epidermal cells (EC), Ficoll-enriched for LC (greater than 10%), were incubated with monoclonal antibodies (MoAb) specific for the adhesion molecules CD11a (LFA-1 alpha), CD18 (LFA-1 beta), or ICAM-1; staining was evaluated by fluorescence microscopy. After 12 h of culture only HLA-DR+ cells (LC) expressed CD11a, CD18, and ICAM-1. As a test for the functional relevance of such adhesion molecule expression, we examined the capacity of the above MoAb to block LC stimulation of alloreactive T cells: EC were co-cultured with allogeneic peripheral blood mononuclear leukocytes (PBML) for 5 d in the presence or absence of MoAb; proliferation was measured by [3H]-thymidine uptake. MoAb against CD11a, CD18, or ICAM-1 reduced the allostimulatory capacity of LC by greater than 70%; combinations of these MoAb reduced proliferation even more (90%). We conclude that interaction of adhesion molecules on LC with ligands on T cells is required for optimal allo-antigen-dependent T-cell activation, perhaps by delivering accessory signals.
Simon
J C
JC
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235-9069.
Cruz
P D
PD
Tigelaar
R E
RE
Sontheimer
R D
RD
Bergstresser
P R
PR
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D004817:Epidermis / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1