Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.
Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.
Herouet
C
C
Clinical Research Unit, Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany.
Cottin
M
M
LeClaire
J
J
Enk
A
A
Rousset
F
F
D000826:Animal Testing Alternatives; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D052160:Benzothiazoles; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion; D002460:Cell Line / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology*; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000276:immunology / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II / Q000187:drug effects*; D006241:Haptens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D016130:Immunophenotyping; D007509:Irritants / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000633:toxicity*; D012965:Sodium Chloride / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D013844:Thiazoles / Q000633:toxicity*
D015703:Antigens, CD; D000954:Antigens, Surface; D052160:Benzothiazoles; D006241:Haptens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007509:Irritants; D013844:Thiazoles; C045305:2,4-dinitrofluorobenzene sulfonic acid; D010081:Oxazolone; D012967:Sodium Dodecyl Sulfate; D012965:Sodium Chloride; C028000:dibenzothiazyl disulfide; D004139:Dinitrofluorobenzene; D004121:Dimethyl Sulfoxide