Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207.
Dendritic cells are professional antigen-presenting cells that initiate primary immunity. Migration from sites of antigen uptake to lymphoid organs is crucial for the generation of immune responses. We investigated the migratory pathways specifically of epidermal Langerhans cells by tracing them from the epidermis to the draining lymph nodes. This was possible with a new monoclonal antibody, directed against murine Langerin/CD207, a type II lectin specific for Langerhans cells. In situ, resident, and activated Langerhans cells express Langerin in the epidermis and on their way through dermal lymphatic vessels. Both emigrated and trypsinization-derived Langerhans cells expressed high levels of Langerin intracellularly but reduced it upon prolonged culture periods. Sizeable numbers of Langerin+ cells were found in skin draining lymph nodes but not in mesenteric nodes. Langerin+ cells localized to the T cells areas and rarely to B cell zones. Numbers of Langerin-expressing cells increased after application of a contact sensitizer. In the steady state, Langerhans cells in the skin-draining nodes expressed maturation markers, such as 2A1 and costimulatory molecules CD86 and CD40. These molecules, CD86 and CD40, were further upregulated upon inflammatory stimuli such as contact sensitization. Thus, the novel anti-Langerin monoclonal antibody permits the unequivocal visualization of migratory Langerhans cells in the lymph nodes for the first time and thereby allows to dissect the relative immunogenic or tolerogenic contributions of Langerhans cells and other types of dendritic cells.
Stoitzner
Patrizia
P
Department of Dermatology, University of Innsbruck, Innsbruck, Austria. patrizia.stoitzner@uibk.ac.at
Holzmann
Sandra
S
McLellan
Alexander D
AD
Ivarsson
Lennart
L
Stössel
Hella
H
Kapp
Michaela
M
Kämmerer
Ulrike
U
Douillard
Patrice
P
Kämpgen
Eckhart
E
Koch
Franz
F
Saeland
Sem
S
Romani
Nikolaus
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D016922:Cellular Senescence; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D020405:Dermis / Q000166:cytology; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000166:cytology; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000737:chemistry / Q000166:cytology*; D037181:Lectins, C-Type / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology*; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology; D014162:Transfection
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins