Expansion of inhibitory NK cell receptor-expressing CD8 T cells and immunoregulatory CD4 T cells

• Project/Area Number: 19591093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: TANAKA Junji Hokkaido University, 大学院・医学研究科, 准教授 (50250452)
• 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: 造血幹細胞移植学 / NK受容体

Research Abstract

同種造血細胞移植においては移植片対宿主病を抑制しつつ、移植片対白血病効果を誘導することがその安全性と有効性において極めて臨床的に重要である。このような理想的な細胞療法を目指して、臍帯血のCD4陽性分画からCD3/CD28ビーズとIL-15, TGF-bを用いて免疫制御性CD25/CD4細胞 (Treg)を、そしてCD4陰性分画からはOKT3とIL-15を用いて抑制性NK細胞受容体(CD94)発現細胞障害性CD8細胞を同時に増幅しうることを明らかにした。

Research Products

• [Journal Article] Regimen-related mucosal injury of the gut increased the incidence of CMV disease after allogeneic bone marrow transplantation (2009)
  • Author(s): Shigematsu A, Yasumoto A, Yamamoto S, Sugita J, Kondo T, Onozawa M, Kahata K, Endo T, Ota S, Sato N, Takahata M, Okada K, Tanaka J, Hashino S, Nishio M, Koike T, Asaka M, Imamura M
  • Journal Title: Biol Blood Marrow Transplant 15 Pages: 679-685
  • NAID: 120001390957
  • Peer Reviewed
• [Journal Article] Serum soluble tumor necrosis factor-related apoptosis-inducing ligand level after allogeneic hematopoietic cell transplantation (2009)
  • Author(s): Toubai T, Shono Y, Tone S, Ibata M, Kato N, Malter C, Lowler KP, Ota S, Tanaka J, Asaka M, Imamura M
  • Journal Title: Leuk Lymphoma 50 Pages: 844-847
  • Peer Reviewed
• [Journal Article] HB vaccination in the prevention of viral reactivation in allogeneic hematopoietic stem cell transplantation recipients with previous HBV infection (2008)
  • Author(s): Onozawa M, Hashino S, Morita R, Takahata M, Shigematsu A, Kahata K, Kondo T, Tanaka J, Imamura M, Asaka M
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 1226-1230
  • NAID: 120001390973
  • Peer Reviewed
• [Journal Article] Ciprofloxacin inhibits lipopolysaccharide-induced toll-like receptor-4 and 8 expression on human monocytes derived from adult and cord blood (2008)
  • Author(s): Kaji M, Tanaka J, Sugita J, Kato N, Ibata M, Shono Y, Ota S, Kondo T, Asaka M, Imamura M
  • Journal Title: Ann Hematol 87 Pages: 229-231
  • NAID: 120000951997
  • Peer Reviewed
• [Journal Article] Effects of the mean daily doses of imatinib during the first year on survival of patients with chronic myeloid leukemia (CML) in Japan : a study of the Hokkaido Hematology Study Group (2008)
  • Author(s): Sugita J, Tanaka J, Kurosawa M, Fukuhara T, Hashino S, Torimoto E, Koizumi K, Masauji N, Nishimura S, Koda K, Imamura M, Kasai M
  • Journal Title: Eur J Haematol 80 Pages: 160-163
  • Peer Reviewed
• [Journal Article] The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive Acute Promyelocytic Leukemia (2008)
  • Author(s): Kondo T, Mori A, Darmanin S, Hashino S, Tanaka J, Asaka M
  • Journal Title: Haematologica 93 Pages: 1414-1416
  • Peer Reviewed
• [Journal Article] T cell receptor excision circle (TREC) levels in CD94-expressing CD8 T Cells during graft-versus-host disease (2008)
  • Author(s): Sugita J, Iwao N, Tanaka J, Kato N, Shiratori S, Wakasa K, Shigematsu A, Toubai T, Takahata M, Kondo T, Asaka M, Imamura M
  • Journal Title: Leukemia Lymphoma 49 Pages: 1306-1310
  • Peer Reviewed
• [Journal Article] HCV non-structural protein 3 and HCV RNA genome in non-Hodgkin lymphoma and transition of the serum HCV RNA level : a retrospective analysis in one institution (2008)
  • Author(s): Shiratori S, Tsutsumi Y, Kawamura T, Kudo K, Shimoyama N, Masauzi N, Tanaka J, Asaka M, Imamura M
  • Journal Title: Int J Hematol 87 Pages: 298-302
  • NAID: 10021256127
  • Peer Reviewed
• [Journal Article] Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total body irradiation for adult patients with acute lymphoblastic leukemia (2008)
  • Author(s): Shigematsu A, Kondo T, Yamamoto S, Sugita J, Onozawa M, Kahata K, Endo T, Shiratori S, Ota S, Obara M, Wakasa K, Takahata M, Takeda Y, Tanaka J, Hashino S, Nishio M, Koike T, Asaka M, Imamura M
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 568-575
  • NAID: 120005906865
  • Peer Reviewed
• [Journal Article] A retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia/lymphoma (ATL) : clinical impact of graft-versus-leukemia/lymphoma effect (2008)
  • Author(s): Shiratori S, Yasumoto A, Tanaka J, Shigematsu A, Yamamoto S, Nishio M, Hashino S, Morita R, Takahata M, Onozawa M, Kahata K, Kondo T, Ota S, Wakasa K, Sugita J, Koike T, Asaka M, Kasai M, Imamura M
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 817-823
  • NAID: 120005906874
  • Peer Reviewed
• [Journal Article] Influence of conditioning regimens and stem cell sources on donor-type chimerism early after stem cell transplantation (2008)
  • Author(s): Sugita J, Tanaka J, Hashimoto A, Shiratori S,Yasumoto A, Wakasa K, Kikuchi M, Shigematsu A, Miura Y, Tsutsumi Y, Kondo T, Asaka M, Imamura M
  • Journal Title: Ann Hematol 87 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells (2008)
  • Author(s): Kato N, Tanaka J, Sugita J, Toubai T, Miura Y, Ibata M, Shono Y, Ota S, Kondo T, Asaka M, Imamura M
  • Journal Title: Leukemia 21 Pages: 2103-2108
  • Peer Reviewed
• [Journal Article] Excellent outcome of allogeneic hematopoietic stem cell tran splantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total body irradiation for adult patients with acute lymphoblastic leukemia (2008)
  • Author(s): Shigematsu A, Tanaka J, et.al.
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 568-575
  • Peer Reviewed
• [Journal Article] A retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia/lymphoma (ATL) : clinical impact of graft-yersus-leukemia/lymphoma effect (2008)
  • Author(s): Shiratori S, Tanaka J, et.al.
  • Journal Title: Biol Blood Marrow Transplant 14 Pages: 817-823
  • Peer Reviewed
• [Journal Article] Influence of conditioning regimens and stem cell sources on donor-type chimerism early after stem cell transplantation (2008)
  • Author(s): Sugita J, Tanaka J, et.al.
  • Journal Title: Ann Hematol 87 Pages: 1003-1008
  • Peer Reviewed
• [Journal Article] Expansion of NK receptor (CD94/NKG2A)-expressing cytolytic CD8 T cells and CD4^+CD25^+ regulatory T cells from the same cord blood unit (2007)
  • Author(s): Tanaka J, Sugita J, Kato N, Toubai T, Ibata M, Shono Y, Ota S, Kondo T, Kobayashi T, Kobayashi M, Asaka M, Imamura M
  • Journal Title: Exp Hematol 35 Pages: 1562-1566
  • Peer Reviewed
• [Journal Article] Expansion of NK receptor(CD94/NKG2A)-expressing cytolytic CD8 T cells and CD4^+CD25^+ regulatory T cells from the same cord blood unit. (2007)
  • Author(s): Tanaka J, et. al.
  • Journal Title: Exp Hematol 35 Pages: 1562-1566
  • Peer Reviewed
• [Journal Article] Regulation of the expression of MHC class I-related chain A, B(MICA, MICB)via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. (2007)
  • Author(s): Kato N, Tanaka J, et. al.
  • Journal Title: Leukemia 21 Pages: 2103-2108
  • Peer Reviewed
• [Presentation] 同種末梢血幹細胞移植 (2009)
  • Author(s): 田中淳司
  • Organizer: 骨髄バンクコーデイネターブラッュアップ研究
  • Place of Presentation: 札幌
  • Year and Date: 2009-02-06
• [Presentation] NK細胞受容体発現細胞と同種造血細胞移植療法 (2009)
  • Author(s): 田中淳司
  • Organizer: 第31回日本造血細胞移植学会総会
  • Place of Presentation: 札幌
• [Presentation] Expansion of CD4+CD25+ regulatory T cells from cord blood CD4+ cells using the common g-chain cytokine IL-15 (2009)
  • Author(s): Tanaka J, Sugita J, Shigematu A, Shiratori S, Wakasa K, Shigematu A, Takahata M, Kondo T, Asaka M, Imamura M
  • Organizer: 37^<th>Annual Meeting of International Society of Hematology (ISEH)
  • Place of Presentation: Boston, USA
• [Presentation] 造血細胞移植におけるGVHD/GVL制御 (2008)
  • Author(s): 田中淳司
  • Organizer: 第6回Tokushima Stem Cell Transplantation (TSCT)研究会
  • Place of Presentation: 徳島
  • Year and Date: 2008-06-20
• [Presentation] 地区調整医師活動の現況 (2008)
  • Author(s): 田中淳司
  • Organizer: 全国骨髄バンクボランテイアの集いin札幌
  • Place of Presentation: 札幌
  • Year and Date: 2008-05-31
• [Presentation] Expansion of CD4+CD25+regulatory T cells from cord blood CD4+ cells using the common g-chain cytokine IL-15 (2008)
  • Author(s): Tanaka J, SugitaJ, et.al.
  • Organizer: 37^<th> Annual Meeting of International Society of Hematology (ISEH)
  • Place of Presentation: Renaissance Boston Waterfront Hotel, Boston, USA
• [Presentation] 悪性リンパ腫-病態分類と従来の治療法、新しい薬 (2007)
  • Author(s): 田中淳司
  • Organizer: 血液がん~より良い治療とより良い治癒 NPO法人つばさ/骨髄移植推進財団 共催フォーラム
  • Place of Presentation: 札幌
  • Year and Date: 2007-12-01
• [Presentation] 造血細胞移植におけるNK受容体発現細胞の役割 (2007)
  • Author(s): 田中淳司
  • Organizer: 第7回血液疾患先端フォーラム
  • Place of Presentation: 金沢
  • Year and Date: 2007-11-03
• [Presentation] GVHD/GVL制御のおけるNK細胞受容体発現細胞の役割 (2007)
  • Author(s): 田中淳司
  • Organizer: 第69回日本血液学会第49回日本臨床血液学会合同シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] 造血細胞移植後の免疫再構築 (2007)
  • Author(s): 田中淳司
  • Organizer: 第3回東大医科研細胞療法セミナー
  • Place of Presentation: 東京
  • Year and Date: 2007-04-20
• [Presentation] Subpopulations of human NK cells after allogeneic stem cell transplantation (2007)
  • Author(s): Tanaka J, Sugita J, Shigematu A, Shiratori S, Wakasa K, Kondo T, Asaka M, Imamura M
  • Organizer: 36^<th> Annual Meeting of International Society of Hematology (ISEH)
  • Place of Presentation: Humberg, Germany