2001 Fiscal Year Annual Research Report

自己免疫疾患を制御するNK-T細胞分化と機能

Research Project

Project/Area Number	12470050
Research Institution	HOKKAIDO UNIVERSITY
Principal Investigator	小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)
Co-Investigator(Kenkyū-buntansha)	柳川芳毅北海道大学, 遺伝子病制御研究所, 助手 (20322852) 岩渕和也北海道大学, 遺伝子病制御研究所, 助教授 (20184898)
Keywords	NK-T細胞 / 自己免疫 / サイトカイン / Th1とTh2 / CD8分子 / 同系MLR
Research Abstract	1.前年度でNK-T細胞の直接前駆細胞をZAP-70ノックアウトマウス、RAGノックアウトマウス胸腺内に同定し、報告した。前駆細胞はNK1.1^+ CD3^-で、これらをin vitroでNK-T細胞内に分化させることに成功しているが、今年度はMHCクラスI拘束性TCRトランスジェニックマウス(2C)を用い、NK-T細胞分化を解析した。これらのマウスで分化するNK-T細胞は、MHCクラスI分子によって異なる表現形、機能を持つことを初めて明らかにし、報告した。特に、CD8鎖(αα、αβ)の違い、IFN-γ産生能などから、これらNK-T細胞はTh1タイプの自己免疫疾患と関係することが示唆された。 2.同系混合リンパ球反応(MLR)の系で、CD8^+T細胞が主として反応する細胞であること、さらにNK-T細胞が自己APCに対して増殖反応を示すことを初めて明らかにした(論文投稿中)。 3.NK-T細胞の分化に胸腺髄質上皮細胞とのcognate interactionが重要な役割を果たすことを発見し、報告した。 4.NZ系自己免疫マウスで、加齢とともにNK-T細胞が減少し、この減少には自己抗体が関与する結果を得た。また、lpr系自己免疫マウスでは、NK-T細胞の減少が認められないことを明らかにした(論文投稿中)。 5.実験的自己免疫性脳脊髄炎(EAE)をperoxisome proliferator-activated receptor-γのアゴニスにより抑制する新しい治療法を開発し、報告した。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Iwabuchi, K., et al.: "Defective development of NK1.1^+ T cell antigen receptor αβ^+ cells in zeta associated protein 70 null mice with an accumulation of NK1.1^+ CD3^- NK-like cells in the thymus"Blood. 97. 1765-1775 (2001)
[Publications] Ohwatari, R., et al.: "Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener's granulomatosis and relapsing polychondritis"Annals of Otology, Rhinology & Laryngology. 110. 1035-1040 (2001)
[Publications] Ishimori, N., et al.: "Mixed allogeneic chimerism with wild-type strains ameliorated atherosclerosis in apolipoprotein E-deficient mice"J.Leukocyte Biol.. 69. 732-740 (2001)
[Publications] Mishima, M., et al.: "Tolerogen-producing cells in allogeneic bone marrow chimeras established with spontaneously leukemia-prone mice"J.Clin.Exp.Hemathopathol.. 41. 61-68 (2001)
[Publications] Niino, M., et al.: "Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-γ"J.Neuroimmunol.. 116. 40-48 (2001)
[Publications] Kizaki, T., et al.: "Immunomodulation by acute cold stress: activation and apoptosis of murine peritoenal macrophages"Biochem.Biophys.Res.Commun.. 283. 700-706 (2001)
[Publications] Yanagawa, Y., et al.: "Enhancement of stromal cell-derived factor-1α-induced chemotaxis for CD4/8 double positive thymocytes by fibronectin and laminin in mice"Immunology. 104. 43-49 (2001)
[Publications] Watano, K., et al.: "Allograft in flammatory factor-1 augments productions of interleukin-6, -10 and -12 by a mouse macrophage line"Immunology. 104. 307-316 (2001)
[Publications] Kizaki, T., et al.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase by AP-1 in macrophage cell line J774A.1"Biochem.Biophys.Res.Commun.. 289. 1031-1038 (2001)
[Publications] Nagata, J., et al.: "Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats"J.Agr.Food.Chem.. 49. 4965-4970 (2001)
[Publications] Mizumoto, N., et al.: "Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse"Immunobiology. 204. 477-493 (2001)
[Publications] Ohwatari, R., et al.: "Developmental and functional analyses of CD8^+ NK1.1^+ T cells in the class I restricted TCR transgenic mice"Cell.Immunol.. 213. 24-33 (2001)
[Publications] 小野江和則: "免疫応答とNK/NKT細胞"血液フロンティア. 11. 1363-1371 (2001)
[Publications] 岩渕和也他: "胸腺内NK-T細胞の分化経路"日本呼吸器外科学会雑誌. 15. 1-2 (2001)
[Publications] 小野江和則: "運動生理・生化学辞典"大修館書店. 10 (2001)
[Publications] 岩渕和也: "運動生理・生化学辞典"大修館書店. 8 (2001)
[Publications] 小野江和則: "New Mook 眼科,眼の自己免疫疾患"金原出版(印刷中). (2002)
[Publications] Onoe, K. et al.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse, The Netherlands (In press). (2001)
[Publications] 小野江和則: "肝臓移植の実際"日本医学館(印刷中). (2002)
[Publications] 小野江和則: "医学大辞典"医学書院(印刷中). (2002)
[Publications] 小野江和則: "免疫学辞典"東京化学同人(印刷中). (2002)

2001 Fiscal Year Annual Research Report

自己免疫疾患を制御するNK-T細胞分化と機能

Principal Investigator

小野江 和則 北海道大学, 遺伝子病制御研究所, 教授 (40002117)

Research Products

[Publications] Iwabuchi, K., et al.: "Defective development of NK1.1^+ T cell antigen receptor αβ^+ cells in zeta associated protein 70 null mice with an accumulation of NK1.1^+ CD3^- NK-like cells in the thymus"Blood. 97. 1765-1775 (2001)

[Publications] Ohwatari, R., et al.: "Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener's granulomatosis and relapsing polychondritis"Annals of Otology, Rhinology & Laryngology. 110. 1035-1040 (2001)

[Publications] Ishimori, N., et al.: "Mixed allogeneic chimerism with wild-type strains ameliorated atherosclerosis in apolipoprotein E-deficient mice"J.Leukocyte Biol.. 69. 732-740 (2001)

[Publications] Mishima, M., et al.: "Tolerogen-producing cells in allogeneic bone marrow chimeras established with spontaneously leukemia-prone mice"J.Clin.Exp.Hemathopathol.. 41. 61-68 (2001)

[Publications] Niino, M., et al.: "Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-γ"J.Neuroimmunol.. 116. 40-48 (2001)

[Publications] Kizaki, T., et al.: "Immunomodulation by acute cold stress: activation and apoptosis of murine peritoenal macrophages"Biochem.Biophys.Res.Commun.. 283. 700-706 (2001)

[Publications] Yanagawa, Y., et al.: "Enhancement of stromal cell-derived factor-1α-induced chemotaxis for CD4/8 double positive thymocytes by fibronectin and laminin in mice"Immunology. 104. 43-49 (2001)

[Publications] Watano, K., et al.: "Allograft in flammatory factor-1 augments productions of interleukin-6, -10 and -12 by a mouse macrophage line"Immunology. 104. 307-316 (2001)

[Publications] Kizaki, T., et al.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase by AP-1 in macrophage cell line J774A.1"Biochem.Biophys.Res.Commun.. 289. 1031-1038 (2001)

[Publications] Nagata, J., et al.: "Effects of water-soluble hemicellulose from soybean hull on serum antibody levels and activation of macrophages in rats"J.Agr.Food.Chem.. 49. 4965-4970 (2001)

[Publications] Mizumoto, N., et al.: "Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse"Immunobiology. 204. 477-493 (2001)

[Publications] Ohwatari, R., et al.: "Developmental and functional analyses of CD8^+ NK1.1^+ T cells in the class I restricted TCR transgenic mice"Cell.Immunol.. 213. 24-33 (2001)

[Publications] 小野江和則: "免疫応答とNK/NKT細胞"血液フロンティア. 11. 1363-1371 (2001)

[Publications] 岩渕和也 他: "胸腺内NK-T細胞の分化経路"日本呼吸器外科学会雑誌. 15. 1-2 (2001)

[Publications] 小野江和則: "運動生理・生化学辞典"大修館書店. 10 (2001)

[Publications] 岩渕和也: "運動生理・生化学辞典"大修館書店. 8 (2001)

[Publications] 小野江和則: "New Mook 眼科,眼の自己免疫疾患"金原出版(印刷中). (2002)

[Publications] Onoe, K. et al.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse, The Netherlands (In press). (2001)

[Publications] 小野江和則: "肝臓移植の実際"日本医学館(印刷中). (2002)

[Publications] 小野江和則: "医学大辞典"医学書院(印刷中). (2002)

[Publications] 小野江和則: "免疫学辞典"東京化学同人(印刷中). (2002)

小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)

[Publications] 岩渕和也他: "胸腺内NK-T細胞の分化経路"日本呼吸器外科学会雑誌. 15. 1-2 (2001)