Accumulation of Metal-Specific T Cells in Inflamed Skin in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis

Abstract

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.

Immunology of metal allergies

“…Yet, other studies comparing multiple metal allergens – including nickel, cobalt and palladium – have reported a close correlation between skin reactivity and the expression of Th2 cytokines in ACD, and found metal allergens to induce a mixed Th1/Th2 response (Figure c). In a recently published novel mouse model of CHS to chromium, which required co‐application of LPS during sensitization, there was a similar Th2‐dominated response towards chromium . However, in light of the above‐mentioned CHS results with MHC II‐deficient mice, the observed correlation of metal reactivity and Th2 polarization may also reflect a proportional counter response to Tc1/Th1 induction (Figure ) as suggested by the coinduction of IL‐10 by those cells shown to inhibit Th1 cytokine expression without affecting Th2 cytokine production .…”

Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

“…Based on these previous reports, our novel murine models of allergies against metals such as Pd, Ni, and Cr were induced through sensitization by administration of metal chlorides and LPS into the mouse groin followed by challenge with several kinds of metal chlorides in the footpad of mice [ 8 , 9 , 10 ]. In our metal allergic mouse models, we found significant differences between ICD and ACD.…”

“…The footpad swelling was reduced at seven days after challenge in ICD mice. However, the footpad swelling continued for 14 days after challenge in ACD mice [ 10 ]. We found that both types of contact dermatitis could not be differentiated by the macroscopic appearance because footpad swelling was the same in both mouse models at one day after challenge.…”

Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy

“…The expression levels of immune response-related genes, including T cell-related CD antigens, cytokines, and cytotoxic granules, were measured by qPCR using the Bio-Rad CFX96 system (Bio-Rad, Hercules, CA, USA). Specific primers for GAPDH, CD3, CD4, CD8, CD14, CD80, IL-1β, IFN-γ, TNF-α, IL-4, IL-5, IL-12, and HDC have been described previously [ 7 , 49 , 50 ]. Freshly isolated total RNA from the footpads of mice was converted to complementary DNA (cDNA).…”

“…Adverse skin reactions to metal ions, such as intractable dermatitis, pustulosis palmaris et plantaris, and incompatibility reactions to metal-containing biomaterials are serious problems [ 2 , 3 , 4 ]. It has been suggested that metal allergy is associated with the infiltration of lymphocytes into sites of allergic inflammation [ 5 , 6 , 7 , 8 ]. Among metals in biomaterials, palladium (Pd), which is frequently used in industry, jewelry, surgical instruments, dental implants [ 9 ], and dental materials (it is a common constituent of dental restorative alloys for crowns and bridges) [ 10 , 11 ], causes metal allergy [ 12 ].…”