The molecular mechanism in the development of pathogenic T-cell through HTLV-1 in HTLV-1-associated myelopathy(HAM)

• Project/Area Number: 22790833
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: ARAYA Natsumi 聖マリアンナ医科大学, 医学(系)研究科(研究院), 助教 (80440353)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: HTLV-1 / HAM / Tax / IFN-γ

Research Abstract

In HTLV-1 associated myelopathy(HAM), the pathogenesis is known as HTLV-1 infected CD4^+T-cells triggered hyper immune response, which leads to chronic inflammation of the central nervous system. In this study, it was demonstrated that HTLV-1 Tax induced the inflammatory cytokine IFN-γproduction through the transcriptional activation of T-bet in HTLV-1 infected CD4^+CD25^+CCR^4+T-cells. These results suggested that HTLV-1 infection-induced IFN-g producing cells resulting in plasticity of infected cells may play an important role in the development and pathogenesis of HAM.

Research Products

• [Journal Article] HTLV-1関連脊髄症(HAM)の治療法を確立していくために-その現状と展望- (2012)
  • Author(s): 山野嘉久、佐藤知雄、安藤仁、新谷奈津美、八木下尚子
  • Journal Title: 日本臨牀 Volume: 70(4) Pages: 705-713
• [Journal Article] Overexpression of SPACIA1/SAAL1, a new gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans (2011)
  • Author(s): 佐藤知雄、中島利博, 他11名
  • Journal Title: Arthritis Rheum Volume: 63 Issue: 12 Pages: 3833-3842
  • DOI: 10.1002/art.30617
  • Peer Reviewed
• [Journal Article] Advantage ofhigher-avidity CTL specific for Taxagainst human T-lymphotropic virus-1 infected cells and tumors. (2011)
  • Author(s): Kitazono T., Araya N., Yamano Y.,et al.
  • Journal Title: Cell Immunol Volume: 272(1) Issue: 1 Pages: 11-17
  • DOI: 10.1016/j.cellimm.2011.10.002
  • Peer Reviewed
• [Journal Article] Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease. (2011)
  • Author(s): Araya N., Sato T., Yagishita N., et al.
  • Journal Title: Viruses Volume: 3 Issue: 9 Pages: 1532-1548
  • DOI: 10.3390/v3091532
  • Peer Reviewed
• [Journal Article] Human T-lymphotropic virus type 1 (HTLV-1) and innate immunity (2011)
  • Author(s): Sato T., Azakami K., Ando H., Araya N., Yamano Y
  • Journal Title: Inflammation and Regeneration Volume: 31 Issue: 1 Pages: 110-115
  • DOI: 10.2492/inflammregen.31.110
  • NAID: 130004943766
  • ISSN: 1880-8190, 1880-9693
  • Peer Reviewed
• [Journal Article] Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type1-associated neurological disease (2011)
  • Author(s): Araya N., Takahashi K., Sato T., Nakamura T., Sawa C., Hasegawa D., Ando H., Aratani S., Yagishita N., Fujii R., Oka H., Nishioka K., Nakajima T., Mori N., Yamano Y
  • Journal Title: Antivir Ther Volume: 16(1) Pages: 89-98
  • Peer Reviewed
• [Journal Article] Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes (2011)
  • Author(s): Sato T, Konomi K, Fujii R, Aono H, Aratani S, Yagishita N, Araya N, Yudoh K, Beppu M, Yamano Y, Nishioka K, Nakajima T
  • Journal Title: Ann Rheum Dis Volume: 70 Issue: 1 Pages: 221-22
  • DOI: 10.1136/ard.2009.118620
  • Peer Reviewed
• [Journal Article] HTLV-1関連脊髄症(HAM)の病態と治療 (2011)
  • Author(s): 安藤仁、八木下尚子、新谷奈津美、佐藤知雄、山野嘉久
  • Journal Title: 医療と検査機器・試薬 Volume: 34(4) Pages: 472-477
• [Journal Article] HAM専門外来の取り組み (2011)
  • Author(s): 山野嘉久、佐藤知雄、新谷奈津美、安藤仁、八木下尚子
  • Journal Title: 神経内科 Volume: 75(4) Pages: 387-392
• [Journal Article] HTLV-1関連脊髄症(HAM)の病態と治療 (2011)
  • Author(s): 安藤仁, 他
  • Journal Title: 医療と検査機器・試薬別冊機器・試薬 Volume: 34(4) Pages: 472-477
• [Journal Article] Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes. (2011)
  • Author(s): Sato T., et al.
  • Journal Title: Ann Rheum Dis Volume: 70(1) Pages: 221-226
  • Peer Reviewed
• [Journal Article] Fucoidan therapy decreases the proviral load in patients with human T-lymphotropic virus type1-associated neurological disease. (2011)
  • Author(s): Araya N., et al.
  • Journal Title: Antivir Ther Volume: 16(1) Pages: 89-98
  • Peer Reviewed
• [Journal Article] E3 ubiquitin ligase synoviolin is involved in liver fibrogenesis (2010)
  • Author(s): Hasegawa D, Fujii R, Yagishita N, Matsumoto N, Aratani S, Izumi T, Azakami K, Nakazawa M, Fujita H, Sato T, Araya N, Koike J, Tadokoro M, Suzuki N, Nagata K, Senoo H, Friedman SL, Nishioka K, Yamano Y, Itoh F, Nakajima T
  • Journal Title: PLoS One Volume: 5 Issue: 10 Pages: e13590-e13590
  • DOI: 10.1371/journal.pone.0013590
  • Peer Reviewed
• [Journal Article] E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis. (2010)
  • Author(s): Hasegawa D., et al.
  • Journal Title: PLoS One Volume: 5(10)
  • Peer Reviewed
• [Journal Article] Human T-lymphotropic virus type 1 (HTLV-1) and innate immunity.
  • Author(s): Sato T., et.al
  • Journal Title: Inflammation and Regeneration Volume: (in press)
  • Peer Reviewed
• [Presentation] The molecular mechanism in the plasticity of HTLV-1 infected CD4+CD25+CCR4+T-cells through HTLV-1 in HAM/TSP (2011)
  • Author(s): Araya N., Sato T., Utsunomiya A., Ando H., Yagishita N., Kannagi M., Tanaka Y., Yamano Y
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉県千葉市(幕張メッセ)
  • Year and Date: 2011-11-27
• [Presentation] Frequency and functional significance ofγδT cells in HTLV-1-infected individuals.(HTLV-1感染者におけるガンマデルタT細胞の頻度および機能的重要性) (2011)
  • Author(s): Sato T., Muto M., Araya N., Kojo S., Maekawa R., Utsunomiya A., Seino K., Yamano Y
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉県千葉市(幕張メッセ)
  • Year and Date: 2011-11-27
• [Presentation] Frequency and functional significance of γ δ T cells in HTLV-1-infected individuals (2011)
  • Author(s): Sato T., et al
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県千葉市)
  • Year and Date: 2011-11-27
• [Presentation] The molecular mechanism in the plasticity of HTLV-1 infected CD4+CD25+CCR4+ T-cells through HTLV-1 in HAM/TSP (2011)
  • Author(s): Araya N., et al
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県千葉市)
  • Year and Date: 2011-11-27
• [Presentation] HTLV-1関連脊髄症(HAM)におけるHTLV-1を介した病原性T細胞発生機構の解析 (2011)
  • Author(s): 新谷奈津美、佐藤知雄、安藤仁、八木下尚子、神奈木真理、田中勇悦、宇都宮與、山野嘉久
  • Organizer: 第4回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京都(東京大学弥生講堂)
  • Year and Date: 2011-09-19
• [Presentation] 出雲周二HTLV-1関連脊髄症(HAM)の臨床病型:臨床経過と検査所見に基づいた分類 (2011)
  • Author(s): 山野嘉久、佐藤知雄、新谷奈津美、八木下尚子、安藤仁、宇都宮與
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京都(東京大学弥生講堂)
  • Year and Date: 2011-09-19
• [Presentation] HTLV-1感染者に適用可能なガンマデルタT細胞療法の開発 (2011)
  • Author(s): 佐藤知雄、武藤真人、新谷奈津美、八木下尚子、前川隆司、宇都宮與、神奈木真理、清野研一郎、山野嘉久
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京都(東京大学弥生講堂)
  • Year and Date: 2011-09-19
• [Presentation] HTLV-1感染者に適用可能なガンマデルタT細胞療法の開発 (2011)
  • Author(s): 佐藤知雄, 他
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京大学弥生講堂(東京都)
  • Year and Date: 2011-09-19
• [Presentation] HTLV-1関連脊髄症(HAM)の臨床病型:臨床経過と検査所見に基づいた分類 (2011)
  • Author(s): 山野嘉久, 他
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京大学弥生講堂(東京都)
  • Year and Date: 2011-09-19
• [Presentation] HTLV-1関連脊髄症(HAM)におけるHTLV-1を介した病原性T細胞発生機構の解析 (2011)
  • Author(s): 新谷奈津美, 他
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京大学弥生講堂(東京都)
  • Year and Date: 2011-09-19
• [Presentation] The plasticity of HTLV-1 infected CD4+CD25+CCR4+T-cells through HTLV-1 tax in HAM/TSP (2011)
  • Author(s): Araya N., Sato T., Utsunomiya A., Ando H., Yagishita N., Kannagi M., Nakamura T., Tanaka Y., Jacobson S., Yamano Y
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Lauderdale, U. S. A
  • Year and Date: 2011-06-05
• [Presentation] Possibility ofγδT cell immunotherapy for HTLV-1-infected individuals (2011)
  • Author(s): Sato T., Muto M., Araya N., Maekawa R., Suzuki N., Utsunomiya A., Seino K., Yamano Y
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Leuven, Belgium(Aula Pieter De Somer)
  • Year and Date: 2011-06-05
• [Presentation] Clinical subtype of HAM/TSP based on clinical course and laboratory findings (2011)
  • Author(s): Yamano Y., Sato T., Araya N., Yagishita N., Shimizu Y., Ando H., Utsunomiya A., Izumo S., Jacobson S., Suzuki N
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Leuven, Belgium(Aula Pieter De Somer)
  • Year and Date: 2011-06-05
• [Presentation] Clinical subtype of HAM/TSP based on clinical course and laboratory findings (2011)
  • Author(s): Yamano Y., et al
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Aula Pieter De Somer (Leuven, Belgium)
  • Year and Date: 2011-06-05
• [Presentation] Possibility of γ δ T cell immunotherapy for HTLV-1-infected individuals (2011)
  • Author(s): Sato T., et al
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Aula Pieter De Somer (Leuven, Belgium)
  • Year and Date: 2011-06-05
• [Presentation] The plasticity of HTLV-1 infected CD4+CD25+CCR4+ T-cells through HTLV-1 tax in HAM/TSP (2011)
  • Author(s): Araya N., et al
  • Organizer: 15th International Conference on Human Retrovirology : HTLV and Related Viruses
  • Place of Presentation: Aula Pieter De Somer (Leuven, Belgium)
  • Year and Date: 2011-06-05
• [Presentation] HTLV-1関連脊髄症(HAM)患者でのフコイダン療法によるウイルス量の減少 (2011)
  • Author(s): 山野嘉久、新谷奈津美、佐藤知雄、中村龍文、森直樹、鈴木登
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 愛知県名古屋市(名古屋国際会議場)
  • Year and Date: 2011-05-20
• [Presentation] HTLV-1関連脊髄症(HAM)患者でのフコイダン療法によるウイルス量の減少 (2011)
  • Author(s): 山野嘉久, 他
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2011-05-20
• [Presentation] HAMの重症度別治療指針に資する疾患活動性バイオマーカーの有用性とステロイド治療による反応性 (2011)
  • Author(s): 山野嘉久
  • Organizer: 平成22年度厚生労働省科学研究費補助金 難知性疾患克服研究事業「HAMの新規バイオマーカー同定による重症度別治療指針の作成と病因細胞標的治療法の開発」平成22年度第2回合同班会議
  • Place of Presentation: 鹿児島(鶴陵会館)
  • Year and Date: 2011-01-08
• [Presentation] HTLV-関連脊髄症(HAM)におけるIFN-γ+CD4+CD25+CCR4+病原性T細胞発生の分子機構解析 (2010)
  • Author(s): 新谷奈津美、佐藤知雄、安藤仁、宇都宮與、山野嘉久
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 庫県神戸市(神戸国際会議場)
  • Year and Date: 2010-12-08
• [Presentation] HTLV-関連脊髄症(HAM)におけるIFN-γ+CD4+CD25+CCR4+病原性T細胞発生の分子機構解析 (2010)
  • Author(s): 新谷奈津美, 他
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸(神戸国際会議場)
  • Year and Date: 2010-12-08
• [Presentation] HTLV-1 promotes the plasticity of HTLV-1 infected T-cells through the regulation of T-bet transcriptional activation in HAM/TSP (2010)
  • Author(s): Araya N., Sato T., Utsunomiya A., Jacobson S. Yamano Y
  • Organizer: Viruses, Genes and Cancer 2010
  • Place of Presentation: Venezia, Italy(Palazzo Cavalli Franchetti)
  • Year and Date: 2010-10-01
• [Presentation] The plasma levels of soluble IL-2 receptor and CXCL10 are useful indicators for disease activity in patients with HAM/TSP (2010)
  • Author(s): Sato T., Araya N., Suzuki N., Yamano Y
  • Organizer: Viruses, Genes and Cancer 2010
  • Place of Presentation: Venezia, Italy(Palazzo Cavalli Franchetti)
  • Year and Date: 2010-10-01
• [Presentation] HTLV-1 infected CD4+CD25+CCR4+ T-cells disregulate balance of inflammation and tolerance in HTLV-1 associated neuroinflammatory disease. (2010)
  • Author(s): Yamano Y.
  • Organizer: Viruses, Genes and Cancer 2010
  • Place of Presentation: Venezia, Italy (Palazzo Cavalli Franchetti)
  • Year and Date: 2010-10-01
• [Presentation] The plasma levels of soluble IL-2 receptor and CXCL10 are useful indicators for disease activity in patients with HAM/TSP. (2010)
  • Author(s): Sato T., et al.
  • Organizer: Viruses, Genes and Cancer 2010
  • Place of Presentation: Venezia, Italy (Palazzo Cavalli Franchetti)
  • Year and Date: 2010-10-01
• [Presentation] HTLV-1 promotes the plasticity of HTLV-1 infected T-cells through the regulation of T-bet transcriptional activation in HAM/TSP. (2010)
  • Author(s): Araya N., et al.
  • Organizer: Viruses, Genes and Cancer 2010
  • Place of Presentation: Venezia, Italy (Palazzo Cavalli Franchetti)
  • Year and Date: 2010-10-01
• [Presentation] HAMの疾患活動性血中バイオマーカーの同定およびステロイドの長期予後改善効果に関する検討 (2010)
  • Author(s): 佐藤知雄、新谷奈津美、安藤仁、山野嘉久
  • Organizer: 第3回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HAMにおけるIFN-γ+CD4+CD25+CCR4+病原性T細胞の発生機構とその脊髄炎症病巣へのリクルート機構に関する解析 (2010)
  • Author(s): 山野嘉久、佐藤知雄、新谷奈津美、安藤仁、神奈木真理、田中勇悦、宇都宮與
  • Organizer: 第3回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HLA-A2トランスジェニックマウスをもちいたTax特異的細胞障害性T細胞の解析 (2010)
  • Author(s): 北薗貴子、岡崎貴裕、新谷奈津美、山野嘉久、山田恭暉、田中勇悦、井上誠、尾崎承一
  • Organizer: 第3回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京(東京大学医科学研究所
  • Year and Date: 2010-08-29
• [Presentation] HLA-A2トランスジェニックマウスをもちいたTax特異的細胞障害性T細胞の解析 (2010)
  • Author(s): 北薗貴子, 他
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HAMにおけるIFN-γ+CD4+CD25+CCR4+病原性T細胞の発生機構とその脊髄炎症病巣へのリクルート機構に関する解析 (2010)
  • Author(s): 山野嘉久, 他
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HAMの疾患活動性血中バイオマーカーの同定およびステロイドの長期予後改善効果に関する検討 (2010)
  • Author(s): 佐藤知雄, 他
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HTLV-関連脊髄症(HAM)におけるHTLV-1 taxを介したIFN-γ+CD4+CD25+CCR4+病原性T細胞発生機構の解析 (2010)
  • Author(s): 新谷奈津美, 他
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京(東京大学医科学研究所)
  • Year and Date: 2010-08-29
• [Presentation] HAMにおける血中sIL-2RとIP-10のバイオマーカーとしての有用性 (2010)
  • Author(s): 山野嘉久、佐藤知雄、新谷奈津美、鈴木登
  • Organizer: HAMにおける血中sIL-2RとIP-10のバイオマーカーとしての有用性
  • Place of Presentation: 東京(東京国際フォーラム)
  • Year and Date: 2010-05-21
• [Presentation] HAMにおける血中sIL-2RとIP-10のバイオマーカーとしての有用性 (2010)
  • Author(s): 山野嘉久, 他
  • Organizer: 第51回日本神経学会
  • Place of Presentation: 東京(東京国際フォーラム)
  • Year and Date: 2010-05-21
• [Presentation] HTLV-関連脊髄症(HAM)におけるHTLV-1 taxを介したIFN-γ+CD4+CD25+CCR4+病原性T細胞発生機構の解析 (2010)
  • Author(s): 新谷奈津美、佐藤知雄、神奈木真理、田中勇悦、宇都宮與、山野嘉久
  • Organizer: 第3回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京(東京大学医科学研究所)
• [Book] T-Cell Leukemia (2011)
  • Author(s): Sato T., Araya N., Yagishita N., Ando H., Yamano Y.
  • Total Pages: 234
• [Book] T-Cell Leukemia (2011)
  • Author(s): Sato T., et al
  • Publisher: InTech
• [Remarks]
  • URL: http://nanchiken.jp/
• [Remarks]
  • URL: http://nanchiken.jp/
• [Remarks]
  • URL: http://www.marianna-u.ac.jp/ims/index.htm
• [Patent(Industrial Property Rights)] HTLV-I関連脊髄症の予防及び/又は治療のための医薬 (2010)
  • Inventor(s): 山野嘉久、佐藤知雄、新谷奈津美
  • Industrial Property Rights Holder: 聖マリアンナ医科大学
  • Filing Date: 2010-04-16
• [Patent(Industrial Property Rights)] HTLV-I 関連脊髄症の予防及び/又は治療のための医薬 (2010)
  • Inventor(s): 山野嘉久、佐藤知雄、新谷奈津美
  • Industrial Property Rights Holder: 聖マリアンナ医科大学
  • Industrial Property Number: 2010-094641
  • Filing Date: 2010-04-16