Novel therapeutic approach for multiple sclerosis using TGF-β-positive regulatory T cell

• Project/Area Number: 19590995
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: OCHI Hirofumi Kyushu University, 大学病院, 講師 (20325442)
• Co-Investigator(Kenkyū-buntansha): 小副川 学 九州大学, 大学病院, 助教 (60380614)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 神経病態免疫学 / 多発性硬化症 / 免疫調節性細胞 / TGF-β / 脳由来神経栄養因子

Research Abstract

健常者の末梢血中におけるLAP陽性CD4+T細胞は1%未満であり、極めて少数の細胞群であった。健常者と比較して多発性硬化症(multiplesclerosis : MS)患者における量的変化を明らかにすることはできなかった。また、MS患者において病期による明らかな差異を見出すこともできなかった。末梢血LAP陽性CD4+T細胞は極めて少数であり、ex vivoでサイトカイン産生能やサプレッサー機能解析を行うことは極めて困難であった。このことから、MSの病態制御にLAP陽性T細胞を臨床応用する場合には、in vitroにおいてヒトLAP陽性T細胞を効率良く誘導し、その機能維持を図ることが重要であると考えられた。
また、末梢血単球からの脳由来神経栄養因子(brain-derived neurotrophic factor : BDNF)産生低下が、MSの障害度進行に関与する可能性を指摘した。

Research Products

• [Journal Article] Research Committee of Neuroimmunological Diseases. Temporal changes and geographical differences in multiple sclerosis phenotypes in Japanese : nationwide survey results over 30 years (2009)
  • Author(s): Osoegawa M, Kira J, FukazawaT, Fujihara K, Kikuchi S, Matsui M, Kohriyama T, Sobue G, Yamamura T, Itoyama Y, Saida T, Sakata K, Ochi H, Matsuoka T
  • Journal Title: Mult Scler 15(2) Pages: 159-73
  • Peer Reviewed
• [Journal Article] Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody (2009)
  • Author(s): Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, Kira J
  • Journal Title: Mult Scler 15(3) Pages: 304-10
  • Peer Reviewed
• [Journal Article] Association of the HLA- DPB1*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders (2009)
  • Author(s): Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara M, Shi N, Nishimura Y, Ochi H, Kira J.
  • Journal Title: Tissue Antigens 73(2) Pages: 171-6
  • Peer Reviewed
• [Journal Article] New immunosuppressive approaches : oral administration of CD3-specific antibody to treat autoimmunity (2008)
  • Author(s): Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso A, Wu H, Chen ML, Gandhi R, Miller A, Maron R, Weiner HL.
  • Journal Title: J Neurol Sci 274(1-2) Pages: 9-12
  • Peer Reviewed
• [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings (2008)
  • Author(s): Matsuoka T, Matsushita T, Osoegawa M, Ochi H, Kawano Y, Mihara F, Ohyagi Y, Kira J
  • Journal Title: J Neurol Sci 266(1-2) Pages: 115-25
  • Peer Reviewed
• [Journal Article] Intrathecal upregulation of IFN-gamma and MIP-lbeta in juvenile muscular atrophy of the distal upper extremity (2008)
  • Author(s): Tanaka M, Ishizu T, Ochi H, Kawano Y, Ohyagi Y, Kira J
  • Journal Title: J Neurol Sci 275(1-2) Pages: 74-7
  • Peer Reviewed
• [Journal Article] Distinct CSF cytokine/chemokine profiles in atopic myelitis and other causes of myelitis (2008)
  • Author(s): Tanaka M, Matsushita T, Tateishi T, Ochi H, Kawano Y, Mei FJ, Minohara M, Murai H, Kira JI
  • Journal Title: Neurology 71(13) Pages: 974-81
  • Peer Reviewed
• [Journal Article] New immunosuppressive approaches : oral administration of CD3-specificantibody to treat autoimmunity. (2008)
  • Author(s): Ochi H, Abraham M, Ishikawa H., et al
  • Journal Title: J Neurol Sci. 274 Pages: 9-12
  • Peer Reviewed
• [Journal Article] Intrathecal upregulation of IFN-gamma and MlP-1beta in juvenile muscular atrophy of the distal upper extremity (2008)
  • Author(s): Tanaka M, Ishizu T, Ochi H, et al
  • Journal Title: J Neurol Sci. 275 Pages: 74-77
  • Peer Reviewed
• [Journal Article] Distinct CSF cytokine/chemokine profiles in atopic myelitis and othercauses of myelitis. (2008)
  • Author(s): Tanaka M, Matsushita T, Tateishi T, Ochi H, et al
  • Journal Title: Neurology 71 Pages: 974-981
  • Peer Reviewed
• [Journal Article] Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings (2008)
  • Author(s): Matsuoka T, Matsushita T, et. al.
  • Journal Title: J Neurol Sci 266 Pages: 115-125
  • Peer Reviewed
• [Journal Article] Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody (2007)
  • Author(s): Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL
  • Journal Title: Diabetes 56(8) Pages: 2103-9
  • Peer Reviewed
• [Journal Article] Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese (2007)
  • Author(s): Matsuoka T, Matsushita T, Kawano Y, Osoegawa M, Ochi H, Ishizu T, Minohara M, Kikuchi H, Mihara F, Ohyagi Y, Kira J.
  • Journal Title: Brain 130 Pages: 1206-23
  • Peer Reviewed
• [Journal Article] Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody (2007)
  • Author(s): Ishikawa H, Ochi H, et. al.
  • Journal Title: Diabetes 56(8) Pages: 2103-2109
  • Peer Reviewed
• [Journal Article] Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese (2007)
  • Author(s): Matsuoka T, Matsushita T, et. al.
  • Journal Title: Brain 130(Pt5) Pages: 1206-1223
  • Peer Reviewed
• [Presentation] 末梢血免疫担当細胞におけるbrain derived neurotrophic factor(BDNF)産生能と多発性硬化症(MS)病態との関連 (2009)
  • Author(s): 吉村怜、越智博文、松岡健、松下拓也、河野祐治、三野原元澄、吉良潤一
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 末梢血免疫担当細胞におけるbrain derived neurotrophic factor (BDNF)産生能と多発性硬化症(MS)病態との関連. (2009)
  • Author(s): 吉村怜, 越智博文, 松岡健, ほか
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 通常型多発性硬化症の病態機序と治療多発性硬化症(MS)病態へのbrain derived neurotrophic factor(BDNF)の関与 (2008)
  • Author(s): 吉村怜、越智博文、松岡健、松下拓也、河野祐治、三野原元澄、吉良潤一
  • Organizer: 第20回日本神経免疫学会学術集会
  • Place of Presentation: 新潟
• [Presentation] New immunosuppressive approaches (2007)
  • Author(s): Ochi H.
  • Organizer: European Charcot Foundation Symposium 2007
  • Place of Presentation: Fiuggi,Italy
  • Year and Date: 2007-11-30
• [Presentation] New immunosuppressive aproaches (2007)
  • Author(s): Ochi H
  • Organizer: European Charcot Foundation Symposium 2007
  • Place of Presentation: Fiuggi, Italy
  • Year and Date: 2007-11-30
• [Presentation] 腸管免疫と全身免疫のクロストークからみた実験的自己免疫性脳脊髄炎の制御 (2007)
  • Author(s): 越智博文、吉良潤一、Weiner Howard
  • Organizer: 第19回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
• [Presentation] 経口抗CD3抗体による実験的自己免疫性脳脊髄炎の抑制 (2007)
  • Author(s): 越智博文、吉良潤一、Weiner Howard
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋