Possible involvement of invariant natural killer T cells and mucosal-associated invariant T cells in a murine model of titanium allergy

Abstract Objective Titanium alloy has long been regarded as a biocompatible material, and is widely used for implants in medicine and dentistry. Titanium is thought to be a potential cause of metal allergy, however, accumulating T cells during development of titanium allergy have been poorly characterized because basic research based on a suitable animal model has not been performed. This study aimed to investigate the skewing of the T-cell receptor repertoire and cytokine profiles of accumulated T cells in inflamed skin during titanium allergy. Methods A novel model of titanium allergy was induced by two sensitizations by injection of TiCl 3 plus lipopolysaccharide solution into the mouse groin followed by two challenges with TiCl 3 into the footpad. Cytokine expression profiles, T cell phenotypes, and T-cell receptor repertoire were determined in the titanium-induced allergic footpads. Results Significant swelling and pathological features, such as spongiosis of the dermis, were histologically evident at 7 days after challenge in mice with titanium allergy. Characterization of the TCR repertoire revealed the presence of the TRAV10/TRAJ18 clonotype, indicative of natural killer T cells, and TRAV1/TRAJ33, associated with mucosal-associated invariant T (MAIT) cells in the inflamed skin of both the irritant and allergic mice models. Conclusions Our murine model of titanium-induced hypersensitivity shows that NKT cells and MAIT cells participate in titanium allergy.