MHC-DEPENDENT AND MHC-INDEPENDENT ACTIVATION OF HUMAN NICKEL-SPECIFICCD8(-CELLS FROM ALLERGIC DONORS() CYTOTOXIC T)

T lymphocytes are critical effectors in the pathogenesis of contact hy persensitivity. Nickel is the most common contact sensitizer in humans and nickel-specific CD4+ T helper cells have been extensively charact erized. Because recent observations have suggested the activation of C D8+ T cells in murine models of contact hypersensitivity, we investiga ted the existence of CD8+ hapten-specific T lymphocytes in patients wi th allergy to nickel. Nickel-specific T cell lines were generated from the peripheral blood of three allergic donors. The T cell lines were composed of a majority of CD4+ T cells, but CD8+ T cells were also pre sent and their percentage increased with repeated in vitro stimulation s. In addition to nickel-reactive helper T cell-0-type or helper T cel l-2-type CD4+ T cell clones, CD8+ T cell clones could be derived from these cell lines and a total of 15 clones were further studied. Cytoki ne production was evaluated for 11 CD8+ T cell clones that were either cytotoxic T cell-0- or cytotoxic T cell-1-type clones. Additional eff ector functions were investigated on the complete panel of T cell clon es. These CD8+ T cells did not only display hapten-specific proliferat ion, but also specific cytotoxic activities towards autologous EBV-B c ells in the presence of nickel. Two different types of CD8+ T cells we re characterized. Most of the clones lysed only autologous targets in the constant presence of nickel; however, one clone was able to lyse n umerous targets in the presence of NiSO4, irrespective of the expressi on of either major histocompatibility complex class I or class II mole cules. The characterization of nickel-specific cytotoxic CD8+ T cells with different requirements for nickel-specific target lysis, may have important implications in the development or in the control of human contact hypersensitivity reactions to nickel in vivo.