NKG2D⁺ IFN-γ⁺ CD8⁺ T cells are responsible for palladium allergy

• Published in: PloS one Vol. 9; no. 2; p. e86810
• Main Authors: Kawano, Mitsuko, Nakayama, Masafumi, Aoshima, Yusuke, Nakamura, Kyohei, Ono, Mizuho, Nishiya, Tadashi, Nakamura, Syou, Takeda, Yuri, Dobashi, Akira, Takahashi, Akiko, Endo, Misato, Ito, Akiyo, Ueda, Kyosuke, Sato, Naoki, Higuchi, Shigehito, Kondo, Takeru, Hashimoto, Suguru, Watanabe, Masamichi, Watanabe, Makoto, Takahashi, Tetsu, Sasaki, Keiichi, Nakamura, Masanori, Sasazuki, Takehiko, Narushima, Takayuki, Suzuki, Ryuji, Ogasawara, Kouetsu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2014; Public Library of Science (PLoS)
• Subjects: Adoptive Transfer; Aging; Allergies; Animal tissues; Animals; Apoptosis; beta 2-Microglobulin - metabolism; Biology; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chromium; Cloning; Cobalt; Contact dermatitis; Dentistry; Dermatitis; Dermatitis, Contact - immunology; Disease; Drainage; Engineering schools; Hepatitis; Hypersensitivity; Hypersensitivity (delayed); Interferon; Interferon-gamma - metabolism; Jewelry; Ligands; Lymph; Lymph nodes; Lymphocytes; Lymphocytes T; Medicine; Metals; Metals - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Mice, Transgenic; Nickel; NK Cell Lectin-Like Receptor Subfamily K - metabolism; Palladium; Palladium - immunology; Rheumatology; T cell receptors; Transgenic mice; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086810

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.