title: NKG2D⁺ IFN-γ⁺ CD8⁺ T cells are responsible for palladium allergy.
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 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.
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan ; Department of Materials Processing, Graduate School of Engineering, Tohoku University, Aramakiaza, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Aoshima
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ono
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nishiya
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Syou
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan ; Graduate School of Dentistry, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Dobashi
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Endo
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Materials Processing, Graduate School of Engineering, Tohoku University, Aramakiaza, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Shigehito
authors.initials: S
authors.lastname: Higuchi
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Graduate School of Dentistry, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Graduate School of Dentistry, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Graduate School of Dentistry, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Graduate School of Dentistry, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Institute for Advanced Study, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.affiliation: Department of Materials Processing, Graduate School of Engineering, Tohoku University, Aramakiaza, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Narushima
authors.affiliation: Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Minami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008024:Ligands; D008670:Metals / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D010165:Palladium / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: C527086:Klrk1 protein, mouse; D008024:Ligands; D008670:Metals; D055655:NK Cell Lectin-Like Receptor Subfamily K; D001613:beta 2-Microglobulin; D010165:Palladium; D007371:Interferon-gamma