Nickel allergy in mice: enhanced sensitization capacity of nickel at higher oxidation states.
Attempts to induce contact hypersensitivity to nickel in mice using, e.g., Ni(II)Cl2 often failed. Here, we report that sensitization was achieved by injecting Ni(II)Cl2 in combination with either CFA or an irritant, such as SDS and PMA, or IL-12, or by administering nickel at higher oxidation states, i.e., Ni(III) and Ni(IV). Although Ni(II), given alone, was ineffective in T cell priming, it sufficed for eliciting recall responses in vivo and in vitro, suggesting that Ni(II) is able to provide an effective signal 1 for T cell activation, but is unable to provide an adequate signal 2 for priming. Immunization of mice with nickel-binding proteins pretreated with Ni(IV), but not with Ni(II), allowed them to generate nickel-specific CD4+ T cell hybridomas. Ni(II) sufficed for restimulation of T cell hybridomas; in this and other aspects as well, the hybridomas resembled the nickel-specific human T cell clones reported in the literature. Interestingly, restimulation of hybridomas did not require the original Ni(IV)-protein complex used for priming, suggesting either that the nickel ions underwent ligand exchange toward unknown self proteins or peptides or that nickel recognition by the TCR is carrier-independent. In conclusion, we found that Ni(III) and Ni(IV), but not Ni(II) alone, were able to sensitize naive T cells. Since both Ni(III) and Ni(IV) can be generated from Ni(II) by reactive oxygen species, released during inflammation, our findings might explain why in humans nickel contact dermatitis develops much more readily in irritated than in normal skin.
Division of Immunology, Medical Institute of Environmental Hygiene and Dermatology Clinic, Heinrich Heine University, Düsseldorf, Germany. artik@uni-duesseldorf.de
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Artik
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Gleichmann
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Schwarz
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004431:Ear, External; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008670:Metals / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012882:Skin Tests
D018984:Epitopes, T-Lymphocyte; D008670:Metals; D016693:Receptors, Antigen, T-Cell, alpha-beta; D009532:Nickel