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New Technologies to Prevent and Treat Contact Hypersensitivity Responses

Abstract: Allergic contact dermatitis is a common inflammatory skin disease caused by T cells that recognize environmental and industrial allergens (i.e., haptens). Langerhans' cells (LC), which are skin‐specific and “immature” members of the dendritic cell (DC) family of antigen‐presenting cells, play crucial roles in the induction of contact hypersensitivity (CH) responses. Upon exposure to haptens, LC migrate from the epidermis to draining lymph nodes, mature into T cell‐stimulatory DC, and activate hapten‐reactive T cells. Therefore, CH responses should be preventable at the sensitization phase by interfering with one of these changes that occur in LC. Our objective is to develop new technologies for the prevention and treatment of allergic contact dermatitis. In this article, we will introduce three technologies that we have recently developed. First, using a phage display strategy, we have identified a 12‐mer peptide (termed “peptide 1”) that binds and blocks the function of hyaluronan (HA), which is known to serve as an adhesive substrate for LC migration. Local injection of peptide 1 in mice before topical application of DNFB blocked almost completely the emigration of LC from the epidermis to the draining lymph node, where antigen presentation takes place. Peptide 1 represents a new strategy that is designed to inhibit the initial event of CH. Second, we have established an in vitro experimental system to study the terminal maturation of LC during antigen‐specific interaction with T cells. This experimental system, which employs a long‐term LC line and T cell clones, should provide a unique tool for the identification of new immunosuppressive agents that block LC terminal maturation selectively. Finally, under the hypothesis that LC, which are engineered to overexpress a death ligand, would deliver apoptotic signals instead of activation signals to T cells, we created a “killer” LC clone by introducing CD95L cDNA into our long‐term LC line XS106. In vivo administration of DNFB‐pulsed killer LC into mice, either before or after sensitization, resulted in marked suppression of CH responses to DNFB. The killer LC technology represents an entirely new immunosuppressive therapy that is designed to eliminate only the pathogenic T cells.