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

Mitsuko Kawano, Masafumi Nakayama, Yusuke Aoshima, Kyohei Nakamura, Mizuho Ono, Tadashi Nishiya, Syou Nakamura, Yuri Takeda, Akira Dobashi, Akiko Takahashi, Misato Endo, Akiyo Ito, Kyosuke Ueda, Naoki Sato, Shigehito Higuchi, Takeru Kondo, Suguru Hashimoto, Masamichi Watanabe, Makoto Watanabe, Tetsu TakahashiKeiichi Sasaki, Masanori Nakamura, Takehiko Sasazuki, Takayuki Narushima, Ryuji Suzuki, Kouetsu Ogasawara

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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 metalresponsive 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.

Original languageEnglish
Article numbere86810
JournalPloS one
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 12 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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