Human MHC restricted T cell generation using thymic organoid

• Project/Area Number: 20200069
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Immunology; Developmental biology
• Research Institution: Kyoto University
• Principal Investigator: HAMAZAKI Yoko 京都大学, 医学研究科, 准教授 (10362477)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥31,850,000 (Direct Cost: ¥24,500,000、Indirect Cost: ¥7,350,000); Fiscal Year 2010: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2009: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2008: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: T細胞分化 / 胸腺 / 上皮細胞 / ヒトT細胞誘導 / 表皮細胞

Research Abstract

In this study, we tried to generate MHOrestricted human T cells in vltroby ccrcultureing human pre-T cells and human keratinocytes. We succeeded in forming thymic organoid; however, failed to induce functional T cells.

Research Products

• [Journal Article] Claudin-4 isinduced in thymocytes of late CD4/CD8 doublepositive stage by E2A and promotes abT cellreceptor.mediated positive selection (2011)
  • Author(s): Kawai. K. Hamazaki, Y., Fujita, H., Fujita,A., Sato, T., Moriwaki, K., Furuse, M., Fujimoto,T., Agata, Y. and Minato, N
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 108(10) Issue: 10 Pages: 4075-4080
  • DOI: 10.1073/pnas.1014178108
  • Peer Reviewed
• [Journal Article] Spa-1 (Sipa1) controlsthe invasion and metastasis of human prostatecancers via Rap signal (2011)
  • Author(s): Shimizu Y, Hamazaki Y, Hattori M, Doi K,Terada Y, Kobayashi T, Toda Y, Yamasak T,Inoue T, Kajita Y, Atsushi M, Kamba T, MikamiY, Kamoto T, Yamada T, Ogawa O, Minato Nand Nakamura E
  • Journal Title: Cancer Science Volume: 102 Issue: 4 Pages: 828-836
  • DOI: 10.1111/j.1349-7006.2011.01876.x
  • Peer Reviewed
• [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency (2011)
  • Author(s): Tanaka H, Tamura A, Sekai M, Hamazaki Y, Minato N
  • Journal Title: Cancer science Volume: 102 Issue: 4 Pages: 784-791
  • DOI: 10.1111/j.1349-7006.2011.01850.x
  • Peer Reviewed
• [Journal Article] Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency (2011)
  • Author(s): Kawai Y, Hamazaki Y, Fujita H, Fujita A, Sato T, Furuse M, Fujimoto T, Jetten AM, Agata Y, Minato N
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(10) Pages: 4075-80
  • Peer Reviewed
• [Journal Article] SPA-1 controls the invasion and metastasis of human prostate cancer (2011)
  • Author(s): Shimizu Y, Hamazaki Y, Hattori M, Doi K, Terada N, Kobayashi T, Toda Y, Yamasaki T, Inoue T, Kajita Y, Maeno A, Kamba T, Mikami Y, Kamoto T, Yamada T, Kanno T, Yoshikawa K, Ogawa O, Minato N, Nakamura E
  • Journal Title: Cancer Sci Volume: 102(4) Pages: 828-36
  • NAID: 10029292527
  • Peer Reviewed
• [Journal Article] Increased c-Myc activity and DNA damage in hematopoietic progenitors precede myeloproliferative disease in Spa-1-deficiency (2011)
  • Author(s): Tanaka H, Tamura A, Sekai M, Hamazaki Y, Minato N
  • Journal Title: Cancer Sci Volume: 102(4) Pages: 784-91
  • NAID: 10029292347
  • Peer Reviewed
• [Journal Article] Memoryphenotype PD-1+ CD4+ T cells expressing C/EBPa underlie T cell immunodepression in senescence and leukemia (2009)
  • Author(s): Shimatani, K., Nakashima, Y., Hattori, M., Hamazaki, Y., and Minato, N
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 106 Issue: 37 Pages: 15807-15812
  • DOI: 10.1073/pnas.0908805106
  • Peer Reviewed
• [Journal Article] Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins (2009)
  • Author(s): Adachi M, Hamazaki Y, Kobayashi Y, Itoh M, Tsukita S, Furuse M, Tsukita S.
  • Journal Title: Mol Cell Biol. Volume: 29(9) Issue: 9 Pages: 2372-89
  • DOI: 10.1128/mcb.01505-08
  • Peer Reviewed
• [Journal Article] Rap signaling is crucial for the competence of IL-7 response and the development of B-lineage cells. (2009)
  • Author(s): Katayama Y, Sekai M, Hattori M, Miyoshi I, Hamazaki Y, Minato N.
  • Journal Title: Blood. Volume: 114 Pages: 1768-1775
  • Peer Reviewed
• [Journal Article] PD-I+memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia. (2009)
  • Author(s): Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 106 Pages: 15807-15812
  • Peer Reviewed
• [Journal Article] Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. (2009)
  • Author(s): Adachi M, Hamazaki Y, Kobayashi Y, Itoh M, Tsukita S, Furuse M, Tsukita S.
  • Journal Title: Mol Cell Biol. 29(9) Pages: 2372-2389
  • Peer Reviewed
• [Journal Article] Rap signaling is crucial for the competence ofIL-7 response and the development of B-lineagecells (2008)
  • Author(s): Katayama, Y., Sekai, M., Hattori, M.,Miyoshi, I., Hamazaki, Y, and Minato, N
  • Journal Title: Blood Volume: 114 Issue: 9 Pages: 1768-1775
  • DOI: 10.1182/blood-2009-03-213371
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • Organizer: RCAI Seminar Series 2011
  • Place of Presentation: 理化学研究所 免疫・アレルギー科学総合研究センター(RCAI)横浜
  • Year and Date: 2012-02-23
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • Author(s): 濱崎洋子
  • Organizer: RCAI Seminar Series 2011
  • Place of Presentation: 理化学研究所免疫・アレルギー科学総合研究センター(RCAI)(招待講演)
  • Year and Date: 2012-02-23
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • Organizer: 特定領域研究(免疫系自己)国際シンポジウムThe 4th Symposium of Immunological Self
  • Place of Presentation: 京都
  • Year and Date: 2012-01-27
• [Presentation] Identification of claudin-expressing medullary thymic epithelial stem cells that maintain the functional medulla during life (2012)
  • Author(s): 濱崎洋子
  • Organizer: 特定領域研究(免疫系自己)国際シンポジウム
  • Place of Presentation: 京都大学紫蘭会館(招待講演)
  • Year and Date: 2012-01-27
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • Author(s): Kyosuke Sato, Suhail Tahir, Yuji Fukushima, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • Author(s): Kyosuke Sato, Suhail Tahir, Yuji Fukushima, Yasuhiro Nakashima, Yoko Hamazaki, Nagahiro Minato
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 千葉(幕張メッセ)
  • Year and Date: 2011-11-29
• [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla (2011)
  • Author(s): Miho Sekai, Yoko Hamazaki and Nagahiro Minato
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-28
• [Presentation] Fetal claudin-3,4 positive mTEC progenitors have the long-term reconstitution capacity of functional thymic medulla (2011)
  • Author(s): Miho Sekai, Yoko Hamazaki, Nagahiro Minato
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 千葉(幕張メッセ)
  • Year and Date: 2011-11-28
• [Presentation] 加齢に伴い増加する新規CD4T 細胞サブセット(T-sen)の同定とその意義 (2011)
  • Organizer: 日本食品免疫学会第7回学術総会
  • Place of Presentation: 東京大学安田講堂 東京
  • Year and Date: 2011-10-19
• [Presentation] 加齢に伴い増加する新規CD4T細胞サブセット(T-sen)の同定とその意義 (2011)
  • Author(s): 濱崎洋子、湊長博
  • Organizer: 日本食品免疫学会第7回学術総会
  • Place of Presentation: 東京(東京大学安田講堂)(招待講演)
  • Year and Date: 2011-10-19
• [Presentation] 自己と非自己を見分ける免疫のしくみ (2011)
  • Organizer: 京大サロントーク
  • Place of Presentation: 京都大学百周年記念館京大サロン 京都
  • Year and Date: 2011-07-12
• [Presentation] 自己と非自己を見分ける免疫のしくみ (2011)
  • Author(s): 濱崎洋子
  • Organizer: 京大サロントーク
  • Place of Presentation: 京大サロン京都(招待講演)
  • Year and Date: 2011-07-12
• [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling (2011)
  • Author(s): Harumi Fujita, Yohei Kawai, Akikazu Fujita, Toyoshi Fujimoto, Mikio Furuse, Yasutoshi Agata, Nagahiro Minato and Yoko Hamazaki
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学 札幌
  • Year and Date: 2011-06-29
• [Presentation] Claudin-4 induction by E-protein activity in thymic lymphocytes and its role in the TCR-mediated signaling (2011)
  • Author(s): Harumi Fujita, Yohei Kawai, Akikazu Fujita, Toyoshi Fujimoto, Mikio Furuse, Yasutoshi Agata, Nagahiro Minato, Yoko Hamazaki
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌(北海道大学)
  • Year and Date: 2011-06-29
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • Author(s): Suhail Tahir, Kyosuke Sato, Yasuhiro Nakashima, Yoko Hamazaki and Nagahiro Minato
  • Organizer: 第10回オステオポンチン研究会
  • Place of Presentation: 北海道大学 札幌
  • Year and Date: 2011-06-19
• [Presentation] A novel CD4+T cell population preferentially producing osteopontin steers altered immune function in senescence and malignancy (2011)
  • Author(s): Suhail Tahir, Kyosuke Sato, Yasuhiro Nakashima, Yoko Hamazaki, Nagahiro Minato
  • Organizer: 第10回オステオポンチン研究会
  • Place of Presentation: 札幌(北海道大学)
  • Year and Date: 2011-06-19
• [Presentation] クローディン４はＥタンパク質の活性によって後期ＤＰ細胞で発現誘導され、ポジティブセレクションの効率化に寄与する (2011)
  • Author(s): 河合洋平、濱崎洋子、藤田春美、縣保年、湊長博
  • Organizer: Kyoto T cell conference
  • Place of Presentation: 京都
  • Year and Date: 2011-06-10
• [Presentation] クローディン4はEタンパク質の活性によって後期DP細胞で発現誘導され、ポジティブセレクションの効率化に寄与する (2011)
  • Author(s): 河合洋平、濱崎洋子、藤田春美、縣保年、湊長博
  • Organizer: Kyoto T cell conference
  • Place of Presentation: 京都(京都平安ホテル)
  • Year and Date: 2011-06-10
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • Place of Presentation: 華中科技大学同済医学院 武漢 中華人民共和国
  • Year and Date: 2011-03-23
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • Author(s): 濱崎洋子
  • Organizer: 華中科技大学同済医学院での招待講演
  • Place of Presentation: 華中科技大学同済医学院武漢中華人民共和国(招待講演)
  • Year and Date: 2011-03-23
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • Place of Presentation: 華中科技大学 武漢 中華人民共和国
  • Year and Date: 2011-03-21
• [Presentation] Claudin expression in the thymus and its implication in T-cell development (2011)
  • Author(s): 濱崎洋子
  • Organizer: 華中科技大学での招待講演
  • Place of Presentation: 華中科技大学武漢中華人民共和国(招待講演)
  • Year and Date: 2011-03-21
• [Presentation] 胸腺組織上皮細胞の発生・分化と自己免疫寛容成立機構の解明 (2011)
  • Organizer: 京都大学優秀女性研究者賞(たちばな賞)受賞講演
  • Place of Presentation: 京都大学医学研究科 紫蘭会館 京都
  • Year and Date: 2011-03-03
• [Presentation] 胸腺組織上皮細胞の発生・分化と自己免疫寛容成立機構の解明 (2011)
  • Author(s): 濱崎洋子
  • Organizer: 京都大学優秀女性研究者賞(たちばな賞)受賞講演
  • Place of Presentation: 京都(京都大学紫蘭会館)(招待講演)
  • Year and Date: 2011-03-03
• [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling (2010)
  • Author(s): Yoko Hamazaki1, Yohei Kawai, Harumi Fujita, Akikazu Fujita, Toyoshi Fujimoto and Nagahiro Minato
  • Organizer: 第62回日本細胞生物学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-05-18
• [Presentation] Tight junction-independent expression of claudin-4 in thymic lymphocytes and its role in TCR-signaling (2010)
  • Author(s): Yoko Hamazakil, Yohei Kawai, Harumi Fujita, Akikazu Fujita, Toyoshi Fujimoto, Nagahiro Minato
  • Organizer: 第62回日本細胞生物学会総会
  • Place of Presentation: 大阪(大阪国際会議場)
  • Year and Date: 2010-05-18
• [Presentation] Claudin-4 expression in thymocytes and its role in T-cell development (2010)
  • Author(s): Yoko Hamazaki, Harumi Fujita, Yohei Kawai and Nagahiro Minato
  • Organizer: An International workshop on T lymphocytes hymOZ
  • Place of Presentation: オーストラリア
  • Year and Date: 2010-03-20
• [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage (2010)
  • Author(s): Miho Sekai, Yoko Hamazaki, Nagahiro Minato
  • Organizer: European Congress of Immunology Liverpool
  • Place of Presentation: UK
• [Presentation] The claudin-3,4 positive mTEC progenitors maintain the potential to generate Aire expressing mTECs over fetal stage (2010)
  • Author(s): Miho Sekai, Yoko Hamazaki, Nagahiro Minato
  • Organizer: European Congress of Immunology
  • Place of Presentation: Liverpool, UK
• [Presentation] Claudin expression in Thymocytes: Implication in T cell Development (2009)
  • Author(s): Yohei Kawai, Yoko Hamazaki, Harumi Fujita and Nagahiro Minato
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Claudin expression in Thymocytes : Implication in T cell Development (2009)
  • Author(s): Yohei Kawai, Yoko Hamazaki, Harumi Fujita, Nagahiro Minato
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Claudin expression in Thymocytes : Implication in T cell Development (2009)
  • Author(s): Yoko Hamazaki, Yohei Kawai, Harumi Fujita, Miho Sekai, Nagahiro Minato
  • Organizer: International Kyoto T cell conference
  • Place of Presentation: 京都大学
  • Year and Date: 2009-06-03
• [Presentation] Claudin expression in thymocytes; Implication in T cell development (2009)
  • Author(s): Yoko Hamazaki, Yohei Kawai, Harumi Fujita, Miho Sekai, and Nagahiro Minato
  • Organizer: The International Workshop on Kyoto T cell Conference
  • Place of Presentation: 京都
• [Presentation] Claudin expression in thymocytes : Implication in T cell development (2008)
  • Author(s): Yoko Hamazaki, Harumi Fujita, Yohei Kawai, Nagahiro Minato
  • Organizer: International Conference on Lymphopoiesis, T cell Differentiation, and Immune Recognition (ThymUS)
  • Place of Presentation: San Juan, Puerto Rico
  • Year and Date: 2008-11-12
• [Presentation] Claudin expression in the thymus: implications in immune function (2008)
  • Organizer: Annual International Workshop on mucosal Immunity for young investigators
  • Place of Presentation: Kiyosato, Japan
• [Book] エッセンシャル免疫学(第2版) (2010)
  • Author(s): 監修笹月健彦
  • Publisher: メディカルサイエンス・インターナショナル
• [Book] 免疫生物学 (2010)
  • Author(s): 監修 笹月健彦
  • Publisher: 南江堂
• [Book] エッセンシャル免疫学(第2版) (2010)
  • Author(s): 監修笹月健彦
  • Total Pages: 552
  • Publisher: メディカル・サイエンス・インターナショナル
• [Book] 免疫生物学第7版 (2010)
  • Author(s): 監修笹月健彦
  • Total Pages: 870
  • Publisher: 南江堂
• [Book] 胸腺の発生 (皮質・髄質上皮細胞の起源と分化)メディカルバイオ (2008)
  • Author(s): 濱崎洋子、湊長博
  • Publisher: オーム社
• [Book] 胸腺上皮細胞に発現するクローディン感染・炎症、免疫 (2008)
  • Author(s): 濱崎洋子、湊長博
  • Publisher: 医薬の門社
• [Book] 胸腺上皮細胞の分化とクローディン医学のあゆみ (2008)
  • Author(s): 濱崎洋子、湊長博
  • Publisher: 医歯薬出版株式会社
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/J/grad_school/introduction/1205/
• [Remarks]
  • URL: http://www.natureasia.com/japan/jobs/tokushu/detail.php?id=505
• [Remarks]
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news7/2010/110303_3.htm
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/J/grad_school/introduction/1205/
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/J/grad_school/introduction/1205/