自己免疫性脱髄疾患の発症機序とその制御に関する免疫分子生物学的研究

• 研究課題/領域番号: 07457155
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 神経内科学
• 研究機関: 信州大学
• 研究代表者: 高 昌星 信州大学, 医学部・附属病院, 講師 (80143981)
• 研究分担者: 井上 敦 信州大学, 医学部, 助手 (50213145)
• 研究期間 (年度): 1995 – 1996
• 研究課題ステータス: 完了 (1996年度)
• 配分額: 7,500千円 (直接経費: 7,500千円); 1996年度: 1,800千円 (直接経費: 1,800千円); 1995年度: 5,700千円 (直接経費: 5,700千円)
• キーワード: 多発性硬化症 / 脱髄 / タイラーウイルス / 抗体 / 接着分子 / 実験的自己免疫性脳脊髄炎 / タイラー脳脊髄炎ウイルス / 免疫寛容

研究概要

我々はTheiler's murine encephalomyelitis virus(TMEV)をSJL/Jマウスの脳に接種し,多発性硬化症の動物実験モデルである免疫性脱髄疾患(TMEV-IDD)を作成することに成功した.さらにTMEV接種時に抗ICAM-1抗体と抗LFA-1の両者を投与することによりTMEV-IDDが抑制されることが明らかとなった.これらは抗接着分子抗体が補助シグナルをブロックすることによりアナ-ジ-が成立し,TMEV抗原特異的免疫寛容が誘導された結果であることが考えられる.さらに我々は個々のcapsid proteinや構造非依存性抗体エピトープを含む合成ペプチドを用いて,タイラーウイルス誘導による免疫性脱髄性疾患(TMEV-IDD)における抗体の役割を検討した.VP1とVP2のfusion proteinで予めマウスを免疫するとその後のタイラーウイルス誘導による免疫性脱髄性疾患の発症を抑制するが,VP3のfusion proteinで予めマウスを免疫してもその後のタイラーウイルス誘導による免疫性脱髄性疾患の発症を抑制しなかった.fusion proteinで予め免疫し,その後のタイラーウイルス誘導による免疫性脱髄性疾患を発症しなかったマウスでは免疫原に相当するcapsid proteinni対する抗体が著明に高かった.これとは対照に,in vitroでウイルスを効果的に中和できる構造非依存性エピトープA1C(VP1262-267)に対する抗体はTMEV-IDDの進行とともに上昇した。さらに個々の抗体エピトープを含む合成ペプチドで免疫することによりエピトープに対する抗体はTMIV-IDDを特異的にかつ効果的に防御することが明らかとなった.以上より,ある特定の構造非依存性エピトープに対する抗体はTMEV-IDDを防ぐことが明らかとなり,この予防効果はウイルス感染の初期に限定される可能性が示唆された.

研究成果

• [文献書誌] Inoue A, et al.: "Anti-adhesion molecule therapy in Theiler's murine encephalomyclitis virus-induced demyelinating disease." Internat Immunol. 9(in press).
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Iwahashi T, et al.: "A study on a new antineural antibody in a case of paraneoplastic sensory neuropathy associated with breast carcinoma." J Neurol Neurosurg Psychiat,. 63. 516-519 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yahikozawa H, el al.: "Major linear antibody epitopes and capsid proteins differentially induce protective immunity against Theiler's virus-induced demyelinating disease." J Virol,. 71. 3105-3113 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yamazaki M, et al: "Phosphatidylserine Suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease." J Neuroimmunol. 75. 113-122 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Inoue A, Koh C-S, et al.: "Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy." J Neuroimmunol. 75. 141-146 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Inoue A, Koh C-S, et al.: "The fibrin deposition in the central nervous system correlates with thedegree of Theiler's murine encephalomyelitis virus-induced demyelinating disease." J Neuroimmunol. 77. 185-194 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Inoue A, Koh C-S, et al.: "The level of tumor necrosis factor-α producing cells in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease." Intermnat Immunol. 8. 1001-1008 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Inoue A, Koh C-S, et al.: "Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewisrats." J Neuroimmunol. 71. 131-137 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hanaoka T,Fujimori M,Shingu K,Hirose S,Maruyama M,Ito K,Asanuma K,Kasuga Y,Kobayashi S,Iwahashi T,Inoue A,Koh C-S,Matsuyama I,Tsuchiya S,Amano J: "A case of occult breast cancer with paraneoplastic polyneuropathy" Breast Cancer. (in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Koh C-S,Takahashi K,Kwaan HC: "Two-color fluorescence analysis of fibrin networks from normal and X-ray irradiated fibrinogens and incorporation of fibrinolytic components by a confocal laser-scanning microscopy" Bioimages. 5. 49-58 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Yamazaki M,Ichikawa M,Isobe M,Ishihara Y,Yagita H,Kim BS: "Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus - induced demyelinating disease" Internat.Immunol.9 (in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Iwahashi T,Koh C-S,inoue A,Yanagisawa N: "Tumor necrosis factor-a and trnasforming growth factor-b production by mononuclear cells in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis" Tohoku J Exp.Med.183. 123-133 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Sakurai S,Inoue A,Koh C-S,Ohwa M,Yanagisawa N: "Soluble form of selectins in blood of patients with acute myocardial infarction and coronary intervention" Vascular Medicine. 2. 163-168 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Iwahashi T,A.Inoue, Koh C-S,N.Yanagisawa: "A sutyd on a new antineural antibody in a case of paraneoplastic sensory neuropathy associated with breast carcinoma" J Neurol.Neurosurg.Psychiat.63. 516-519 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Sekijima Y,Tokuda T,Hashimoto T,Koh C-S,Shoji S,Yanagisawa N: "Serial magnetic resonance imaging (MRI) study of a patient with Balo's concentric sclerosis treated with immunoadsorption plasmapheresis" Multi Scler. 2. 291-294 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yahikozawa H,Inoue A,Koh C-S,Choe Y-K,Kim BS: "Major linear antibody epitopes and capsid proteins differentially induce protective immunity against Theiler's virus-induced demyelinating disease" J Virol.71. 3105-3113 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yamazaki M,Inoue A,Koh C-S,Sakai T,Ishihara Y: "Phosphatidylserine suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease" J Neuroimmunol.75. 113-122 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Sakai T,Yamazaki M,Yanagisawa N,Usuku K,Osame M: "Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy" J Neuroimmunol.75. 141-146 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Yamazaki M,Yanagisawa N,Ishihara Y,Kim BS: "The fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease" J Neuroimmunol.77. 185-194 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yamazaki M,Koh C-S,Inoue A,Yanagisawa N: "Comparative study of the efficacy of plasma exchange, immunoadsorption plasmapheresis and corticosteroid administration for the treatment of Guillain-Barre syndrome" Jpn.J Apheresis.16. 204-205 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Tsuyusaki J,Sakai T,Koh C-S,Yanagisawa N,Arakura H,Oguchi H: "Immunoadsorption plasmapheresis in inflammatory demyelinating disease" Jpn.J Apheresis.16. 206-207 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Yahikozawa H,Yanagisawa N,Yagita H,Ishihara Y,Kim BS: "The level of tumor necrosis factor-Ephi producing cells in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus - induced demyelinating disease." Internat.Immunol.8. 1001-1008 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Yanagisawa N,Taketomi T,Ishihara Y: "Suppression of Theiler's murine encephalomyelitis virus - induced demyelinating disease by administration of gangliosides" J Neuroimmunol.64. 45-53 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Inoue A,Koh C-S,Shimada K,Yanagisawa N,Yoshimura K: "Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats" J Neuroimmunol.71. 131-137 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yamazaki M,et al: "Phosphatidylserine suppresses Theiler′s murine encephalomyelitis virus-induced demyelinating disease." J Neuroimmunol. (in press).
• [文献書誌] Inoue A,Koh C-S,et al: "Detection of the soluble from of the Fas molecule in patients with multiple sclerosis and human T-1ymphotropic virus type I-associated myelopathy." J Neuroimmunol. (in press).
• [文献書誌] Inoue A,Koh C-S,et al: "The fibrin deposition in the central nervous system correlates with the degree of Theiler′s murine encephalomyelitis virus-induced demyelinating disease." J Neuroimmunol. (in press).
• [文献書誌] Sekijima Y,et al: "Serial magnetic resonance imaging(MRI)study of a patient with Bolo′s concentric sclerosis treated with immunoadsorption plasmapheresis." Multiple Sclerosis. (in press).
• [文献書誌] Yahikozawa H,et al: "Major linear antibody epitopes and capsid proteins differentjally induce protective immunity against Theiler′s virus-induced demyelinating disease." J Virol. 71. 3105-3113 (1997)
• [文献書誌] Yamazaki M,Koh C-S,et al: "Comparative study of the efficacy of plasma exchange,immunoadsorption plasmapheresis and corticosteroid administration for the treatment of Guillain-Barre syndrome." Jpn J Apheresis. 16. 204-205 (1997)
• [文献書誌] Inoue A,Tsuyusaki J et al: "Immunoadsorption plasmapheresis in inflammatory demyelinating disease." Jpn J Apheresis. 16. 206-207 (1997)
• [文献書誌] Inoue A,Koh C-S,et al: "The level of tumor necrosis factor-Eφ producing cells in the central nervous system correlates with the degree of Theiler′s murine encephalomyelitis virus-induced demyelinating disease." Internat Immunol. 8. 1001-1008 (1996)
• [文献書誌] Inoue A,Koh C-S,et al: "Suppression of Theiler′s murine encephalomyelitis virus-induced demyelinating disease by administration of gangliosides." J Neuroimmunol. 64. 45-53 (1996)
• [文献書誌] Inoue A,Koh C-S,et al: "Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats." J Neuroimmunol. 71. 131-137 (1996)
• [文献書誌] Sakurai S,et al: "Soluble form of of selectins inblood of patients with acute myocardial infarction and coronary intervention." Vascular Medicine. (in press).
• [文献書誌] Koh C-S,Inoue A,et al: "Combined therapy of corticosteroid and intermittent treatment with immunoadsorption plasmapheresis in polymyositis/dermatomyositis." Jpn J Apheresis. 14. 65-66 (1995)
• [文献書誌] A.Inoue,C.-S.Koh,et al: "Suppression of Theiler′s murine encephalomyelitis virus induced demyelinating disease by administration of gangliosides" Journal of Neuroimmunology. 64. 45-53 (1996)
• [文献書誌] A.Inoue,C.-S.Koh,et al: "The level of tumor necrosis factor-α producing cells in the spinal cord correlates with the degree of Theiler′s murine encephalomyelitis virus-induced demyelinating disease." International Immunology. (印刷中). (1996)
• [文献書誌] C.-S.Koh,A.Inoue,et al: "Immunoadsorption plasmapheresis in Balo′s concentric sclerosis" Japanese Journal of Apheresis. 15. 42-44 (1996)
• [文献書誌] Y.Sekijima,et al: "Serial magnetic resonance imaging(MRI)study of a patient with Balo′s concentric sclerosis treated with immunoadsorption plasmapheresis" Multiple sclerosis. (印刷中). (1996)
• [文献書誌] A.Inoue,C.-S.Koh,et al: "Immunoadsorption plasmapheresis in inflammatory demyelinating diseases" Japanese Journal of Apheresis. (印刷中). (1996)
• [文献書誌] C.-S.Koh,A.Inoue,et al: "The role of immunoadsorption plasmapheresis in chronic inflammatory demyelinating polyneuropathy" Japanese Journal of Apheresis. (印刷中). (1996)