title: Nickel acts as an adjuvant during cobalt sensitization.
abstract: Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal-alloys where nickel and cobalt co-exist. Importantly, very little is known about how co-exposure to nickel and cobalt affects the immune system. We investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear-swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear-swelling and increased B and T cell responses in the draining lymph nodes compared to mice sensitized with cobalt alone. In contrast, the presence of cobalt during nickel sensitization only induced an increased CD8(+) T cell proliferation during challenge to nickel. Thus, the presence of nickel during cobalt sensitization potentiated the challenge response against cobalt more than the presence of cobalt during sensitization to nickel affected the challenge response against nickel. Taken together, our study demonstrates that sensitization with a mixture of nickel and cobalt leads to an increased immune response to both nickel and cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to correlate with the inflammatory properties of the allergen.
authors.affiliation: Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte Menné
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: Morten Milek
authors.initials: MM
authors.lastname: Nielsen
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vennegaard
authors.forename: Jeanne Duus
authors.initials: JD
authors.lastname: Johansen
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Thyssen
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001402:B-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003035:Cobalt / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D009532:Nickel / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D003035:Cobalt; D009532:Nickel
keywords: cobalt; cocktail-effect; contact allergy; nickel