Development of a non-human primate autoimmune model using autoreactive lymphocytes derived from induced pluripotent stem cells

• Project/Area Number: 23659201
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: ITOH Yasushi 滋賀医科大学, 医学部, 准教授 (90324566)
• Co-Investigator(Kenkyū-buntansha): OGASAWARA Kazumasa 滋賀医科大学, 医学部, 教授 (20169163) ; ISHIGAKI Hirohito 滋賀医科大学, 医学部, 助教 (90432301)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: iPS細胞 / リンパ球 / 霊長類モデル / 自己免疫疾患 / 免疫学 / 病理学

Research Abstract

We sought to establish an autoimmune cynomolgus macaque model using autoreactive T lymphocytes derived from iPS cells. iPS cells were derived from fibroblasts in the skin of a cynomolgus macaque. The iPS cells were culture with feeder cells in the medium containing cytokines to induce hematopoietic stem cells. Furthermore, induced hematopoietic like cells were cultured with feeder cells inducing T lymphocyte differentiation in the medium containing cytokines. The cultured cells had T-cell antigen receptors, which were expressed on the surface of mature T lymphocytes. The induced T lymphocytes did not respond to cells from the donor macaque.

Research Products

• [Journal Article] Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine (2013)
  • Author(s): Nakayama M, Shichinohe S, Itoh Y, Ishigaki H, Kitano M, Arikata M, Pham VL, Ishida H, Kitagawa N, Okamatsu M, Sakoda Y, Ichikawa T, Tsuchiya H, Nakamura S, Le QM, Ito M, Kawaoka Y, Kida H, Ogasawara K
  • Journal Title: PLoS ONE Volume: 8 Issue: 12 Pages: e82740-e82740
  • DOI: 10.1371/journal.pone.0082740
  • Peer Reviewed
• [Journal Article] Pathogenicity of pandemic H1N1 influenza A virus in immunocompromised cynomolgus macaques (2013)
  • Author(s): Pham VL, Nakayama M, Itoh Y, Ishigaki H, Kitano M, Arikata M, Ishida H, Kitagawa N, Shichinohe S, Okamatsu M, Sakoda Y, Tsuch -iya H, Nakamura S, Kida H, Ogasawara K
  • Journal Title: PLoS ONE Volume: 8 Issue: 9 Pages: e75910-e75910
  • DOI: 10.1371/journal.pone.0075910
  • Peer Reviewed
• [Journal Article] Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice (2013)
  • Author(s): Kitano M, Kodama M, Itoh Y, Kanazu T, Kobayashi M, Yoshida R, Sato A
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: Vol.57 Issue: 5 Pages: 2286-2294
  • DOI: 10.1128/aac.02324-12
  • Peer Reviewed
• [Journal Article] Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in ynomolgus monkeys carrying Mafa-A*052:02 (2012)
  • Author(s): Arikata M, Itoh Y, Okamatsu M, Maeda T, Shiina T, Tanaka K, Suzuki S, Nakayama M, Sakoda Y, Ishigaki H, Takada A, Ishida H, Soda K, Pham VL, Tsuchiya H, Nakamura S, Torii R, Shimizu T, Inoko H, Ohkubo I, Kida H, Ogasawara K
  • Journal Title: PLos ONE Volume: 7 Issue: 5 Pages: e37220-e37220
  • DOI: 10.1371/journal.pone.0037220
  • Peer Reviewed
• [Journal Article] Efficacy of single intravenous injection of peramivir against influenza B virus infection in ferrets and cynomolgus macaques (2011)
  • Author(s): Kitano M, Itoh Y, Kodama M, Ishigaki H, Nakayama M, Ishida H, Baba K, Noda T, Sato K, Nihashi Y, Kanazu T, Yoshida R, Torii R, Sato A, Ogasawara K
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: Vol.55 Issue: 11 Pages: 4961-4970
  • DOI: 10.1128/aac.00412-11
  • Peer Reviewed
• [Presentation] Pathogenicity of pandemic (H1N1) 2009 influenza A virus in immunosuppressed cynomolgus monkeys (2013)
  • Author(s): Itoh Y, Nakayama M, Ishigaki H, Ogasawara K
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2013-12-12
• [Presentation] Therapeutic efficacy of a human-mouse chimeric anti-H5 hemagglutinin antibody on lethal H5N1 highly pathogenic avian influenza virus infection in cynomolgus macaques (2012)
  • Author(s): Itoh Y, Ishigaki H, Nakayama M, Ishida H, Ogasawara K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2012-12-07
• [Presentation] Influenza virus peptides specifically bound to cynomolgus macaque major histocompatibility complex class I Mafa-A1*5202 (2011)
  • Author(s): Itoh Y, Arikata M, Ishigaki H, Nakayama M, Ishida H, Ogasawara K
  • 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)
  • Year and Date: 2011-11-29
• [Presentation] Identification of pandemic influenza virus NP peptides bound to cynomolgus macaque MHC class I Mafa-A1*5202 and stimulating CTL responses (2011)
  • Author(s): Itoh Y, Arikata M, Maeda T, Shiina T, Ishigaki H, Takada A, Okamatsu M, Sakoda Y, Nakayama M, Kida H, Ogasawara K
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2011-09-15
• [Presentation] Identification of pandemic influenza virus NP peptides bound to cynomolgus macaque MHC class I Mafa-A1*5202 and stimulating CTL responses. (2011)
  • Author(s): Itoh Y, et al.
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター（北海道）
• [Presentation] Influenza virus peptides specifically bound to cynomolgus macaque major histocompatibility complex class I Mafa-A1*5202. (2011)
  • Author(s): Itoh Y, 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）
• [Presentation] Pathogenicity of pandemic (H1N1) 2009 influenza A virus in immunosuppressed cynomolgus monkeys.
  • Author(s): Itoh Y, Nakayama M, Ishigaki H, Ogasawara K
  • Organizer: 第４２回日本免疫学会総会、学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] An inactivated whole particle vaccine induced memory immune responses against pandemic (H1N1) 2009 influenza virus in cynomolgus monkeys carrying Mafa-A1*052:02
  • Author(s): Yasushi Itoh, et al.
  • Organizer: 第１６回日本ワクチン学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Remarks]
  • URL: http://www.shiga-medac.jp/~hqpatho2/
• [Remarks] 滋賀医科大学疾患制御病理学部門研究業績
  • URL: http://www.shga-med.ac.jp/~hqpatho2/publication.html
• [Remarks] 滋賀医科大学疾患制御病理学講座研究業績
  • URL: http://www.shiga-med.ac.jp/~hqpatho2/publications.html