Human epidermal cell-induced generation of alloreactive cytotoxic T-lymphocyte responses against epidermal cells. Requirement for DR-positive Langerhans cells.

Human epidermal cells act as stimulators in the mixed-skin cell lymphocyte culture reaction (MSLR). To analyse the generation in MSLR of alloreactive cytotoxic T lymphocytes (CTL) in cell-mediated cytolysis of human epidermal cells. a phenomenon suggested by various observations of skin inflammatory processes in vivo, 18-h 51Cr-release assays against epidermal cells cultivated on collagen-coated plates (epidermal cells autologous to the stimulator cells in MSLR) were conducted after allogenic human MSLR. To analyse the role of human Langerhans cells and related epidermal dendritic cells, which are the only cells expressing the DR-Ia-like (class II) antigens in normal epidermis and in suspensions of normal epidermal cells, MSLR and CTL assays were conducted with, as stimulator cells, suspensions of normal human epidermal cells as controls, and, in parallel, suspensions of epidermal cells after preincubation with anti-class II monoclonal antibody and complement. The generation of alloreactive CTL to epidermal cells occurred only after allogenic MSLR and when targets and stimulator cells were from the same donor; it was abolished when epidermal cell suspensions used in MSLR were depleted in HLA-DR-expressing cells. These findings demonstrate that an epidermal cell-induced generation of cell-mediated cytotoxicity to human epidermal cells may occur in vitro. Langerhans cells and other class II antigen-expressing epidermal cells (dendritic indeterminate cells) are necessary for an optimal in vitro sensitization in MSLR and the subsequent generation of alloreactive CTL towards epidermal cells in man.