The novel antigen-specific immune regulation for pathogenic CD8+ T cells

• Project/Area Number: 23791109
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kumamoto University
• Principal Investigator: HIRATA Shinya 熊本大学, 大学院・生命科学研究部, 助教 (60418829)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 臨床免疫学 / 筋炎 / ES-DC / 自己免疫疾患 / マウス筋炎 / 抗原特異的免疫制御療法 / CD8陽性T細胞

Research Abstract

It is desirable to develop a therapeutic means to down-modulate immune responses in anantigen-specific manner without causing systemic immune suppression. We tried the immune regulationof pathogenic CD8+ T cells by mouse ES cell-derived dendritic cells (ES-DCs) expressing both antigenand immunosuppressive molecule, such as TRAIL or PD-L1. In this period, we brought in the C-proteininduced myositis, CIM, which was disease model caused by pathogenic CD8+ T cells. The functionalES-DCs expressing immunosuppressive molecule was prepared. These ES-DCs may prevent pathogenicCD8+ T cells-derived autoimmune disease.

Research Products

• [Journal Article] Suppression of elevations in serum C reactive protein levels by anti-IL-6 autoantibodies in two patients with severe bacterial infections (2013)
  • Author(s): Nanki T, Onoue I, Nagasaka K, Takayasu A, Ebisawa M, Hosoya T, Shirai T, Sugihara T, Hirata S, Kubota T, Harigai M, Miyasaka N
  • Journal Title: Ann. Rheum. Dis Volume: 72 Issue: 6 Pages: 1100-1102
  • DOI: 10.1136/annrheumdis-2012-202768
  • Peer Reviewed
• [Journal Article] 臨床免疫・アレルギー科 特集:サイトカインのすべて (2012)
  • Author(s): 平田真哉, 「TRAIL」
  • Journal Title: 科学評論社 (東京) Volume: 54号 Pages: 238-242
• [Journal Article] 筋炎におけるサイトカイン異常 (2012)
  • Author(s): 平田真哉
  • Journal Title: Clinical Neuroscience Volume: 30(3) Pages: 296-300
• [Journal Article] Cytokines in myositis (2012)
  • Author(s): 平田真哉
  • Journal Title: 医学のあゆみ Volume: 別冊 Pages: 53-57
  • NAID: 40019000692
• [Journal Article] Immunotherapy with pluripotent stem cell-derived dendritic cell (2011)
  • Author(s): Senju, S., Matsunaga, Y., Fukushima, S., Hirata, S., Motomura, Y., Fukuma, D., Matsuyoshi, H., Nishimura, Y.
  • Journal Title: Seminars in Immunopathology Volume: 33 Issue: 6 Pages: 603-612
  • DOI: 10.1007/s00281-011-0263-y
  • NAID: 120005199485
  • Peer Reviewed
• [Journal Article] Oligomannose-coatedliposomes efficiently induce humanT-cell leukemia virus-1-specificcytotoxic T lymphocytes withoutadjuvant (2011)
  • Author(s): Kozako, T., Hirata, S., Shimizu, Y.,Satoh, Y., Yoshimitsu, M., White, Y.,Lemonnier, F., Shimeno, H., Soeda, S.and Arima, N
  • Journal Title: FEBS J Volume: 278(8) Issue: 8 Pages: 1358-66
  • DOI: 10.1111/j.1742-4658.2011.08055.x
  • Peer Reviewed
• [Journal Article] Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer (2011)
  • Author(s): Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tomita Y, Tsunoda T, Nakagawa H, Nakamura Y, Baba H, Nishimura Y
  • Journal Title: Br J Cancer Volume: 104 Issue: 2 Pages: 300-307
  • DOI: 10.1038/sj.bjc.6606052
  • Peer Reviewed
• [Journal Article] Peptides derived from human insulin-like growth factor (IGF)-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells (2011)
  • Author(s): Y. Tomita, et al.
  • Journal Title: Cancer Science Volume: 102 Issue: 1 Pages: 71-78
  • DOI: 10.1111/j.1349-7006.2010.01780.x
  • Peer Reviewed
• [Journal Article] 筋炎におけるサイトカイン (2011)
  • Author(s): 平田真哉
  • Journal Title: 医学のあゆみ Volume: 239(1) Pages: 53-57
• [Journal Article] CD8+T 細胞の transcriptionsignature は自己免疫疾患の予後予測に有用である (2011)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 45(3) Pages: 285-290
• [Journal Article] 実験的自己免疫性脳脊髄炎(EAE)と C 蛋白誘導性筋炎(CIM)について (2011)
  • Author(s): 平田真哉,上阪等
  • Journal Title: 免疫疾患-疾患モデルの作製と利用 Pages: 92-97
• [Journal Article] Immunotherapy with pluripotent stem cell-derived dendritic cells. (2011)
  • Author(s): Senju, S., Matsunaga, Y., Fukushima, S., Hirata, S., Motomura, Y., Fukuma, D., Matsuyoshi, H. and Nishimura, Y.
  • Journal Title: Semin Immunopathol Volume: 33(6) Pages: 603-612
  • NAID: 120005199485
  • Peer Reviewed
• [Journal Article] Oligomannose-coated liposomes efficiently induce human T-cell leukemia virus-1-specific cytotoxic T lymphocytes without adjuvant. (2011)
  • Author(s): Kozako, T., Hirata, S., Shimizu, Y., Satoh, Y., Yoshimitsu, M., White, Y., Lemonnier, F., Shimeno, H., Soeda, S. and Arima, N.
  • Journal Title: FEBS J Volume: 278(8) Pages: 1358-1366
  • Peer Reviewed
• [Journal Article] Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer. (2011)
  • Author(s): Imai, K., Hirata, S., Irie, A., Senju, S., Ikuta, Y., Yokomine, K., Harao, M., Inoue, M., Tomita, Y., Tsunoda, T., Nakagawa. H., Nakamura, Y., Baba, H. and Nishimura, Y.
  • Journal Title: Br J Cancer Volume: 104(2) Pages: 300-307
  • Peer Reviewed
• [Journal Article] Peptides derived from human insulin-like growth factor-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells. (2011)
  • Author(s): Tomita, Y., Harao, M., Senju, S., Imai, K., Hirata, S., Irie, A., Inoue, M., Hayashida, Y., Yoshimoto, K., Shiraishi, K., Mori, T., Nomori, H., Kohrogi, H., and Nishimura Y.
  • Journal Title: Cancer Sci Volume: 102(1) Pages: 71-78
  • NAID: 10029288476
  • Peer Reviewed
• [Journal Article] 実験的自己免疫性脳脊髄炎（EAE）とC蛋白誘導性筋炎（CIM）について (2011)
  • Author(s): 平田真哉，上阪等
  • Journal Title: 免疫疾患-疾患モデルの作製と利用 Volume: 1 Pages: 92-97
• [Journal Article] 器質化肺炎 (2011)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 46(5) Pages: 467-471
• [Journal Article] CD8+T細胞のtranscription signatureは自己免疫疾患の予後予測に有用である (2011)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 45(3) Pages: 285-290
• [Presentation] 満屋裕明関節リウマチ治療中にリンパ増殖性疾患を合併した 8 症例の解析 (2012)
  • Author(s): 平田真哉、野坂生郷、宮川英子、星乃光有、奥野豊
  • Organizer: 第56回日本リウマチ学会総会 ・学術集会
  • Place of Presentation: 東京(グランドプリンスホテル新高輪)
  • Year and Date: 2012-04-28
• [Presentation] 自己免疫性筋炎における再生筋線維の役割 (2012)
  • Author(s): 木村直樹、平田真哉、宮坂信之、上阪等
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京 (グランドプリンスホテル新高輪)
  • Year and Date: 2012-04-28
• [Presentation] 自己免疫性筋炎における再生筋線維の役割 (2012)
  • Author(s): 木村直樹、平田真哉、宮坂信之、上阪等
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京、グランドプリンスホテル新高輪
• [Presentation] 関節リウマチ治療中にリンパ増殖性疾患を合併した8症例の解析 (2012)
  • Author(s): 平田真哉
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京、グランドプリンスホテル新高輪
• [Presentation] マウス筋炎モデルにおける再生筋線維が発現するケモカインの役割について (2011)
  • Author(s): 平田真哉
  • Organizer: 第3回筋炎ワークショップ
  • Place of Presentation: 東京(海運クラブ)(招待講演)
  • Year and Date: 2011-10-01
• [Presentation] Chemokinesexpressed by the regenerating musclecells in murine myositis model (2011)
  • Author(s): Shinya Hirata, Naoki Kimura, NaoTateishi, Ayaka Maeda, NobuyukiMiyasaka and Hitoshi Kohsaka
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸(神戸ポートピアホテル)
  • Year and Date: 2011-07-20
• [Presentation] マウス筋炎モデルにおける再生筋線維が発現するケモカインの役割について (2011)
  • Author(s): 平田真哉
  • Organizer: 第3回筋炎ワークショップ(招待講演)
  • Place of Presentation: 東京（海運クラブ）
• [Presentation] Chemokines expressed by the regenerating muscle cells in murine myositis model (2011)
  • Author(s): Shinya Hirata, Naoki Kimura, Nao Tateishi, Ayaka Maeda, Nobuyuki Miyasaka and Hitoshi Kohsaka
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸（神戸ポートピアホテル）