Pathological Analysis of Metal Allergy to Metallic Materials

Abstract

Metal allergy is thought to be caused by the release of ions from metallic materials. Extensive use of metal in jewelry, coins, surgical instruments, and dental restorations may be responsible for recent increases in allergy incidence. Metal allergic disease is categorized as a delayed-type hypersensitivity, which is developed more than 24 h after exposure to the causal metal. The hallmark of delayed-type hypersensitivity is the recruitment of lymphocytes and inflammatory cells, including T cells and granulocytes, to the site of allergic inflammation. During the development of metal allergy, T cells are known to play a role, and since metal ions are thought to function as haptens, T cell-mediated responses likely contribute to allergic disease. While the involvement of pathogenic T cells in the development of metal allergy has not been explored using animal models, studies utilizing human patient samples have been conducted. T cell clones, both CD4+ and CD8+, have been established from peripheral blood mononuclear cells of patients with metal allergy, and their responsiveness to the causal metal has been analyzed. It was found that metal ions induced proliferation of these T cells in vitro and some of the T cell clones produced IFN-γ or IL-4 after metal stimulation, while others produced both T helper 1- and 2-type cytokines. However, the subset of pathogenic T cells involved in the development of metal allergy and their cytokine profiles remain controversial. Recently, a novel animal model that reproduces human metal allergy has been established. Here we show the pathogenesis of metal allergy in the view of immunological responses using this animal model.