Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB.

Abstract

Langerhans cells (LC) have recently been shown to be the only epidermal cells that bear Fc and C3 receptors, and that express Ia antigens on their surface, supporting the hypothesis that LC are an epidermal equivalent of the monocyte-macrophage lineage. Functional in vitro studies have demontrated that antigen-pulsed, Langerhans cell-enriched, epidermal cell preparations can induce proliferative responses in immune T cells that are comparable in magnitude to those induced by similarly pulsed macrophages. Additionally, LC have been linked to cutaneous cell-mediated reactions such as delayed contact hypersensitivity to DNFB and other allergens. Using C57BL/6J mice, we have investigated the induction of contact hypersensitivity to DNFB through normal skin and throughskin deficient in Langerhans cells: Tail skin epidermis is relatively deficient in Langerhans cells compared to normal body wall skin; abdominal body wall skin can be depleted of Langerhans cells via exposure to short course ultraviolet light irradiation. These cutaneous sites were evaluated for their capacity to sustain sensitization to DNFB. The degree of in vivo sensitivity was assessed by measuring ear swelling after challenge with contactant. When sensitization was attempted through 1) normal body wall skin, 2) body wall skin treated with UV irradiation, and 3) normal tail skin, only 1) normal body wall skin supported the induction of sensitization to DNFB. More importantly, animals whose first exposure to DNFB occurred through skin deficient in Langerhans cells were unable subsequently to become specifically sensitized when immunization was attempted through the conventional route using normal body wall skin. We conclude that not only are Langerhans cells essential for induction of contact hypersensitivity to chemical allergens, but in their absence, exposure to these agents leads to specific unresponsiveness.