MHC-dependent and -independent activation of human nickel-specific CD8+ cytotoxic T cells from allergic donors.
T lymphocytes are critical effectors in the pathogenesis of contact hypersensitivity. Nickel is the most common contact sensitizer in humans and nickel-specific CD4+ T helper cells have been extensively characterized. Because recent observations have suggested the activation of CD8+ T cells in murine models of contact hypersensitivity, we investigated the existence of CD8+ hapten-specific T lymphocytes in patients with 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 present and their percentage increased with repeated in vitro stimulations. In addition to nickel-reactive helper T cell-0-type or helper T cell-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. Cytokine production was evaluated for 11 CD8+ T cell clones that were either cytotoxic T cell-0- or cytotoxic T cell-1-type clones. Additional effector functions were investigated on the complete panel of T cell clones. These CD8+ T cells did not only display hapten-specific proliferation, but also specific cytotoxic activities towards autologous EBV-B cells in the presence of nickel. Two different types of CD8+ T cells were characterized. Most of the clones lysed only autologous targets in the constant presence of nickel; however, one clone was able to lyse numerous targets in the presence of NiSO4, irrespective of the expression of either major histocompatibility complex class I or class II molecules. 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.
Moulon
C
C
Max-Planck-Institut for Immunbiology, Freiburg, Germany.
Wild
D
D
Dormoy
A
A
Weltzien
H U
HU
D001782:Blood Donors; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D002999:Clone Cells; D003877:Dermatitis, Contact / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000097:blood; D000949:Histocompatibility Antigens Class II / Q000097:blood; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008285:Major Histocompatibility Complex / Q000276:immunology*; D009532:Nickel / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009532:Nickel