ORAL INDUCTION OF TOLERANCE TO NICKEL SENSITIZATION IN MICE

Antigen contact via the alimentary tract prior to sensitization may re sult in systemic immunologic unresponsiveness (''oral tolerance''). Th e induction of oral tolerance seems an attractive strategy to combat u ndesired immune responses, such as allograft rejection and autoimmune and allergic diseases. We describe clear and reproducible sensitizatio n to nickel in mice reared under nickel-free conditions. Hypersensitiv ity was induced by injecting nickel sulfate intradermally into the fla nk skin and elicited by injecting the metal salt into the pinnae of th e ears. The effectiveness of orally induced hyporesponsiveness could b e inferred from a low degree of hypersensitivity obtained with mice ra ised and maintained in cages with nickel-releasing covers and water ni pples. This mouse model for the assay of nickel hypersensitivity was u sed for oral tolerance studies by administrating non-toxic doses of ni ckel sulfate in drinking water or intragastrically prior to sensitizat ion. In these animals, the development of delayed-type hypersensitivit y was suppressed in a dose-dependent way, and the hyporesponsiveness c ould be transferred by CD8+ cells. The antigen specificity of this ora l tolerance could be demonstrated by the concomitant use of sensitizat ion and challenge procedures for nickel and chromium. The hypersensiti vity assay described provides a versatile, highly reproducible experim ental model to study immunoregulation of oral tolerance to clinically relevant metal allergens.