concanamycin-a and Dermatitis--Allergic-Contact

CD8+ T cells have been assigned a prominent role in allergic contact dermatitis, including nickel allergy; however, human nickel-reactive T cells of the CD8+ phenotype have largely escaped detailed investigation. Here we characterize two quite unusual nickel-specific cytotoxic T cell clones isolated from the peripheral blood of two nickel-sensitized patients. These clones mediate nickel-specific cytolysis of many human cell lines, independent of the expression of HLA class I, CD1, or HLA class II molecules. Lysis is mediated by the alphabeta T cell receptors and involves the perforin, but not the Fas/Fas ligand pathway. Both antigen receptors lack sequence homology to each other as well as to typical natural killer T cell receptors. A transfectant expressing the rearranged alphabeta T cell receptor derived from one of the T cell clones unequivocally demonstrates that the T cell receptor itself is necessary and sufficient to confer HLA-independent nickel specificity. The independent isolation of these clones from two individuals points to an important role of such cells in the pathology of nickel contact dermatitis.

Topics: Anti-Bacterial Agents; CD8 Antigens; CD8-Positive T-Lymphocytes; Clone Cells; Dermatitis, Allergic Contact; Enzyme Inhibitors; Epitopes; Histocompatibility Antigens Class II; Humans; Macrolides; Nickel; Receptors, Antigen, T-Cell, alpha-beta; Strontium; T-Lymphocytes, Cytotoxic; Transfection