Nickel,
cobalt, and
chromium are well known to be causal agents of
allergic contact dermatitis.
Palladium (Pd) can also cause allergic disease and exposure results from wide use of this
metal in dental restorations and jewelry.
Metal allergy is categorized as a delayed-type
hypersensitivity, and
metal-responsive T cell clones have been isolated from allergic patients. However, compared to
nickel, little is known about the pathology of allergic disease mediated by Pd, and pathogenic T cells are poorly understood. To identify the pathogenic T cells that are responsible for onset of Pd
allergy, we enriched
metal-responsive lymphocytes by sequential adoptive transfer of involved lymph node cells. Here we show that sequential adoptive transfer gradually increased the incidence and the intensity of Pd
allergy, and CD8⁺ T cells are responsible for the disease as CD8⁺ T cell-depleted mice and β2-microglobulin-deficient mice did not develop Pd
allergy. In addition, we found that draining lymph node cells skewed toward CD8⁺ T cells in response to Pd challenge in 8th adoptive transferred recipient mice. The CD8⁺ T cells expressed NKG2D, a costimulatory molecule involved in the production of IFN-γ. NKG2D
ligand was also induced in Pd-injected tissues. Furthermore, both NKG2D
ligand-transgenic mice, where NKG2D is downmodulated, and IFN-γ-deficient mice showed impaired Pd
allergy. Taken together, these results indicate that IFN-γ-producing NKG2D⁺ CD8⁺ T cells are responsible for Pd
allergy and suggest that NKG2D is a potential therapeutic target for treatment of
metal allergy.