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.
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.
Ma
J
J
Department of Dermatology, Massachusetts General Hospital, Boston.
Wang
J H
JH
Guo
Y J
YJ
Sy
M S
MS
Bigby
M
M
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
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016650:Fluorescein-5-isothiocyanate