title: In vivo treatment with anti-ICAM-1 and anti-LFA-1 antibodies inhibits contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes.
abstract: Development of contact hypersensitivity in mice depends on the migration of Langerhans cells from the epidermis to regional lymph nodes. Since ICAM-1 and LFA-1 play important roles in leukocyte migration, we sought to determine whether in vivo administration of anti-ICAM-1 and anti-LFA-1 antibodies would inhibit contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes. Twenty-four hours after contact sensitization of mice with FITC, a brightly FITC-stained Ia+ population of dendritic cells capable of stimulating a FITC-specific Ia-restricted T-cell hybridoma was readily detected in their draining lymph nodes. Animals treated with anti-Ia mAb, which depletes Ia+ cells in lymph nodes and spleen but not Ia+ Langerhans cells in the epidermis, had normal numbers of FITC-bearing Ia+ cells capable of stimulating the T-cell hybridoma. Dendritic lymph node cells from mice treated with anti-ICAM-1 and anti-LFA-1 mAb were devoid of brightly FITC-stained cells and cells capable of stimulating the FITC-specific T-cell hybridoma. The combination of anti-ICAM-1 and anti-LFA-1 mAb completely inhibited the induction of contact hypersensitivity to FITC. Animals treated with anti-ICAM-1 or anti-LFA-1 monoclonal antibodies alone had significantly reduced (by 79 and 36%, respectively) numbers of brightly stained cells capable of stimulating the hybridomas. These data suggest that the adhesion molecules, ICAM-1 and LFA-1, play a significant role in contact hypersensitivity-induced migration of Langerhans cells to regional lymph nodes. The immunomodulatory effects of anti-adhesion molecule antibodies in vivo may be in part due to their effects on antigen-presenting cell migration.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Guo
authors.forename: M S
authors.initials: MS
authors.lastname: Sy
authors.forename: M
authors.initials: M
authors.lastname: Bigby
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002465:Cell Movement / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016650:Fluorescein-5-isothiocyanate