Cutaneous tolerance induction : a possible strategy for the treatment of autoimmune disease

Exposure of murine skin to carcinogens such as 7,12- dimethylbenz[a]anthracene (DMBA) or ultraviolet light B (UVB) irradiation depletes the epidermal Langerhans cells (LC) and alters the local environment such that antigen applied through the treated skin causes the development of antigen specific immunosuppression. This ability to induce suppression was used as a strategy to downregulate an established immune response in mice sensitised to a contact sensitiser or mice with autoimmune disease. Mice immune to picryl chloride or 2,4,6-trinitrochlorobenzene (TNCB) were treated with either DMBA or UVB irradiation which was then followed by TNCB through the treated skin. The DMBA followed by TNCB treatment downregulated both contact hypersensitivity (CHS) and antibody production in an antigen specific manner, whereas UVB followed by TNCB treatment could only downregulate the CHS response. When spleen cells were transferred from TNCB tolerant mice (i.e. naive mice treated with DMBA followed by TNCB) to TNCB-immune mice, both an established CHS and an established antibody response were downregulated in an antigen specific manner. Although there was significant downregulation, the reduction was not complete as it did not reach the background level.