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Palladium (Pd) is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause adverse reactions such as hypersensitivity in the oral mucosa. However, the pathological mechanism of intraoral Pd allergies remains unclear because its animal model in the oral mucosa has not been established. In this study, we established a novel murine model of Pd–induced allergies in the oral mucosa, and explored the immune response of cytokine profiles and T cell diversity in terms of the T cell receptor. The Pd–induced allergy mouse was generated by two sensitizations with PdCl2, plus a lipopolysaccharide solution into the postauricular skin followed by a single Pd challenge of the buccal mucosa. Significant swelling and pathological features were histologically evident at five days after the challenge, and CD4–positive T cells producing high levels of T helper 2 type cytokines had accumulated in the allergic oral mucosa. Characterization of the T cell receptor repertoire in Palladium allergic mice indicated that Pd–specific T cell populations were limited in V and J genes but were diverse at the clonal level. Our model demonstrated that a Pd–specific T cell population with Th2 type response tendencies may be involved in the Pd–induced intraoral metal contact allergy. [ABSTRACT FROM AUTHOR]

Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion-induced allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Chromium (Cr) causes delayed-type hypersensitivity reactions possibly mediated by accumulating T cells into allergic inflamed skin, which are called irritants or allergic contact dermatitis. However, accumulating T cells during development of metal allergy are poorly characterized because a suitable animal model is not available. This study aimed to elucidate the skewing of T-cell receptor (TCR) repertoire and cytokine profiles in accumulated T cells in inflamed skin during elucidation of Cr allergy. A novel model of Cr allergy was induced by two sensitizations of Cr plus lipopolysaccharide solution into mouse groin followed by single Cr challenge into the footpad. TCR repertoires and nucleotide sequences of complementary determining region 3 were assessed in accumulated T cells from inflamed skin. Cytokine expression profiles and T-cell phenotypes were determined by qPCR. CD3+CD4+ T cells accumulated in allergic footpads and produced increased T helper 1 (Th1) type cytokines, Fas, and Fas ligand in the footpads after challenge, suggesting CD4+ Th1 cells locally expanded in response to Cr. Accumulated T cells included natural killer (NK) T cells and Cr-specific T cells with VA11-1/VB14-1 usage, suggesting metal-specific T cells driven by invariant NKT cells might contribute to the pathogenesis of Cr allergy. [ABSTRACT FROM AUTHOR]

Metal allergy is usually diagnosed by patch testing, however, the results do not necessarily reflect the clinical symptoms because of cross-reactivity between different metals. In this study, we established the novel mouse model of cross-reactive metal allergy, and aimed to elucidate the immune response in terms of T-cell receptor repertoire. This model was classified into two groups: the sensitization to nickel and challenge with palladium group, and the sensitization to chromium and challenge with palladium group. This model developed spongiotic edema with intra- and peri-epithelial infiltration of CD4+ T cells in the inflamed skin that resembles human contact dermatitis. Using T cell receptor analysis, we detected a high proportion of T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 in the Ni- and Cr-sensitized Pd-challenged mice. Furthermore, mucosal-associated invariant T cells and invariant natural killer T cells were also detected. Our results indicated that T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 induced the development of palladium-cross reactive allergy, and that mucosal-associated invariant T and invariant natural killer T cells were also involved in the cross-reactivity between different metals. [ABSTRACT FROM AUTHOR]