Subtoxic concentrations of allergenic haptens induce LC migration and maturation in a human organotypic skin explant culture model: a novel method for identifying potential contact allergens

• Published in: Experimental dermatology 2006-06, Vol.15 (6), p.421-431
• Main Authors: Lehé, Cynthia L., Jacobs, John J. L., Hua, Chi Mei, Courtellemont, P, Elliott, Graham R., Das, Pranab K.
• Format: Article
• Language: English
• Subjects: activation markers; allergen; Allergens - administration & dosage; Allergens - toxicity; Antigens, CD - metabolism; Biological and medical sciences; CD83 Antigen; Cell Differentiation - drug effects; Cell Movement - drug effects; Dermatitis, Allergic Contact - etiology; Dermatitis, Allergic Contact - immunology; Dermatitis, Allergic Contact - pathology; Dermatology; Haptens - administration & dosage; Haptens - toxicity; HOSEC; Humans; Immunoglobulins - metabolism; Langerhans cell; Langerhans Cells - drug effects; Langerhans Cells - pathology; Langerhans Cells - physiology; Medical sciences; Membrane Glycoproteins - metabolism; migration; Models, Biological; Skin - drug effects; Skin - pathology; Skin - physiopathology; Tissue Culture Techniques
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.0906-6705.2006.00415.x

:  The accelerated migration of Langerhans cells (LCs) out of the epidermis and up‐regulation of maturation markers, upon treatment with subtoxic concentrations of chemicals, were used as the criteria to determine the potential of allergenic chemicals capable of inducing a hapten‐specific delayed‐type hypersensitivity reaction. Here we report the findings of a study in which seven chemicals, coded and tested in a blind fashion, were classified as contact allergens or non‐allergens using the human organotypic skin explant culture (hOSEC) model. All chemicals that were identified as a contact sensitizer on decoding induced a definite decrease in the number of CD1a and HLA‐DR‐positive epidermal LCs in the epidermis of the skin explants, as determined by both semiquantitative immunohistochemistry and quantitative flow cytometric analysis. A significant increase in the number of CD83+ cells was accompanied by up‐regulation of activation molecules in the epidermis of hOSEC exposed specifically to contact allergens. In contrast, there were only minor alterations in epidermal LC numbers, expression of CD83 and other activation markers by LCs when the biopsies were treated with non‐toxic concentrations of non‐allergenic irritants and vehicles. The data suggest that an increased epidermal LC migration and maturation accompanied by increased expression of activation markers could be used as end‐point determinants to screen allergens in a non‐animal alternative hOSEC model.