1996 年度実績報告書

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

研究課題/領域番号	07457155
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)
キーワード	実験的自己免疫性脳脊髄炎 / タイラー脳脊髄炎ウイルス / 多発性硬化症 / 接着分子 / 免疫寛容
研究概要	モルモット髄鞘塩基性蛋白(GPMBP)でSJL/Jマウスを感作し,実験的自己免疫性脳脊髄炎(EAE)を作成することに成功した.GPMBP感作時に接着分子に対する抗体である抗intercellular asdhesion molecule 1(ICAM-1)抗体または抗leukocyte function associated antigen 1(LFA-1)抗体あるいは両者を投与することにより臨床的にも,組織学的にもEAEが抑制できた.抑制効果は抗ICAM-1抗体と抗LFA-1抗体の両者を投与した場合により顕著に現れた.EAEマウスではinterferon γ(IFN-γ)産生細胞が多く,抗ICAM-1抗体または抗LFA-1抗体あるいは両者の投与マウスではIL-4産生細胞がより多い傾向にあり,発症にはTh1細胞が,抑制にはTh2細胞が関与している可能性が示唆された. また我々はTheiler′s murine encephalomyelitis virus(TMEV)をSJL/Jマウスの脳に接種し,免疫性脱髄性脳脊髄炎(TMEV-IDD)を作成することにも成功した.タイラーウイルス誘導による免疫性脱髄性疾患は多発性硬化症の動物実験モデルある.さらにTMEV接種時に抗ICAM-1抗体と抗LFA-1抗体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かとなった.TMEV-IDDはより多発性硬化症に近い動物モデルであり,細胞性免疫が本症の発症にも重要な役割を担っていることが明かとなった.こうした結果は抗接着分子抗体の多発性硬化症における治療法の開発に大きく貢献するものと考えられる.

研究成果
(12件)

すべてその他

すべて文献書誌 (12件)

[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)

1996 年度 実績報告書

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

研究代表者

高 昌星 信州大学, 医学部・附属病院, 講師 (80143981)

研究成果

[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)

1996 年度実績報告書

高昌星信州大学, 医学部・附属病院, 講師 (80143981)