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制御性T細胞による新規慢性GVHD治療法の開発

Research Project

Project/Area Number 17659312
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

小島 勢二  名古屋大学, 大学院医学系研究科, 教授 (20313992)

Co-Investigator(Kenkyū-buntansha) 谷ヶ崎 博  名古屋大学, 医学部附属病院, 助手 (90378141)
鈴木 治彦  名古屋大学, 大学院・医学系研究科, 助教授 (90283431)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords制御性T細胞 / 慢性GVHD / 同種幹細胞移植 / 同種骨髄移植
Research Abstract

本研究の目的は、マウスで発見されたTreg機能を持つCD8^+/CD122^+細胞分画が、ヒトにおいても同様にTreg機能を示すかを、造血幹細胞移植後の臨床検体を用いて検討することである。
1)第3者健常人末梢血単核球(5×10^4)を用いて、リンパ球混合培養(MLR)をおこない、この系に同種幹細胞移植後にCD8^+/CD122^+細胞分画の著増(CD8分画中の89.9%)がみられた患者由来末梢血単核球を添加してMLRを抑制するかを検討した。CD8^+分画(1×10^4)を添加した場合は、MLRを顕著に抑制したが、CD8^-分画ではMLRの抑制が見られなかったことよりCD8^+分画にTreg機能を持つ細胞分画が存在する可能性が示された。
2)同種骨髄移植を施行した26例を対象に移植後、day20,40,60,80,100と継時的にフローサイトメトリーを用いてリンパ球分画におけるCD8^+/CD122^+細胞分画の割合を解析した。Day40,60,80におけるCD8^+/CD122^+分画(%)は、非血縁あるいは肌A不一致血縁ドナー間移植後(n=22)は47.2±33.6%,37.4±28.1%,41.9±31.8%で、HLA一致血縁者間移植(n=4)の12.3±12.4%,22.8±15.2%,13.5±12.3%と比較して、高い傾向がみられた。同様に慢性GVHDが発症した10例と発症がみられない17例とでCD8^+/CD122^+分画の割合をday60,day80とで検討したが、47.3±26.1%vs33.9±24/1%,58.2±34.3%vs30.5±26.3%と慢性GVHDの発症群で高い傾向がみられた。移植後のCD8^+/CD122^+分画の割合は個人差が著しく、今後は多数例においてはCD8^+/CD122^+分画細胞のin vitroにおけるTreg機能を中心にした検討が必要である。

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005

All Journal Article (25 results)

  • [Journal Article] Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RASmutations.2007

    • Author(s)
      Matuda K, Kojima S, et al.
    • Journal Title

      Blood (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia.2007

    • Author(s)
      Hidaka H, Kojima S, et al.
    • Journal Title

      Leuk Res (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pro-inflammatory cytokinemia is frequently found in Down syndrome patients with hematological disorders.2007

    • Author(s)
      Shimada A, Kojima S, et al.
    • Journal Title

      Leuk Res (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ATG投与後のリンパ球の回復パターンは急性および慢性GVHDの発症と関連する。2006

    • Author(s)
      Itzel Bustos, 小島勢二, 他
    • Journal Title

      臨床血液 47(9)

      Pages: 1172-1172

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Preceding immunosuppressive therary with antithymocyte globulin and ciclosporin increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings.2006

    • Author(s)
      Kobayashi R, Kojima S, et al.
    • Journal Title

      Br J Haematol 135(5)

      Pages: 693-693

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical and genetic analyses of presumed Shwachman-Diamond syndrome in Japan.2006

    • Author(s)
      Taneichi H, Kojima S, et al.
    • Journal Title

      Int J Hematol 84(1)

      Pages: 60-60

    • NAID

      10020357843

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Allogeneic haematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation fludarabine and cyclophosphamide in Fanconi anaemia.2006

    • Author(s)
      Yabe H, Kojima S, et al.
    • Journal Title

      Br J Haematol 134(2)

      Pages: 208-208

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of an immunogenic CD8+T-cell epitope derived from gamma-globin,a putative tumor-associated antigen for juvenile myelomonocytic leukemia.2006

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Blood 108(8)

      Pages: 2662-2662

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mutations in telomerase catalytic protein in Japanese children with aplastic anemia.2006

    • Author(s)
      Liang J, Kojima S, et al.
    • Journal Title

      Haematologica 91(5)

      Pages: 656-656

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan.2006

    • Author(s)
      Imamura M, Kojima S, et al.
    • Journal Title

      Int J Hematol 83(2)

      Pages: 164-164

    • NAID

      10017279057

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evaluation of apoptosis in Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis2006

    • Author(s)
      Kawada J, Kojima S, et al.
    • Journal Title

      J Med Virol. 78(3)

      Pages: 400-407

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Current status of hematopoietic cell transplantation for adult patients with hematologic disease and solid tumors in Japan.2006

    • Author(s)
      Imamura M, Kojima S, et al.
    • Journal Title

      Int J Hematol. 83(2)

      Pages: 164-178

    • NAID

      10017279057

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Presence of anti-kinectin and anti-PMS1 antibodies in Japanese aplastic anemia patients.2005

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Br J Haematol. 128(2)

      Pages: 221-223

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection.2005

    • Author(s)
      Kimura H, Kojima S, et al.
    • Journal Title

      J Infect Dis. 191(4)

      Pages: 531-539

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia.2005

    • Author(s)
      Hasegawa D, Kojima S, et al.
    • Journal Title

      Br J Haematol. 128(6)

      Pages: 805-812

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Therapy-related myelodysplastic syndrome in childhood : a retrospective study of 36 patients in Japan.2005

    • Author(s)
      Tsurusawa M, Kojima S, et al.
    • Journal Title

      Leuk Res. 29(6)

      Pages: 625-632

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of DKC1 gene mutations in Japanese patients with X-linked dyskeratosis congenital.2005

    • Author(s)
      Kanegane H, Kojima S, et al.
    • Journal Title

      Br J Haematol. 129(3)

      Pages: 432-434

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.2005

    • Author(s)
      Kratz CP, Kojima S, et al.
    • Journal Title

      Blood. 106(6)

      Pages: 2183-2185

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Leukemic cell death induced by antithymocyte globulin.2005

    • Author(s)
      Yoshimi A, Kojima S, et al.
    • Journal Title

      Reuk Res. 29(7)

      Pages: 821-827

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Engraftment of NOD/SCID gammac(null) mice with multilineage neoplastic cells from patients with juvenile myelodaysplastic leukaemia.2005

    • Author(s)
      Nakamura Y, Kojima S, et al.
    • Journal Title

      Br J Haematol. 130(1)

      Pages: 51-57

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 11th Symposium on Aplastic Anemia and 9th Symposium on Myelodysplastic Syndromes in Children.2005

    • Author(s)
      Manabe A, Kojima S.
    • Journal Title

      Pediatr Int. 47(5)

      Pages: 572-574

    • NAID

      10016939140

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Serial morphologic observation of bone marrow in aplatsic anemia in children.2005

    • Author(s)
      Bessho F, Koj ima S, et al.
    • Journal Title

      Int J Hematol. 81(5)

      Pages: 400-404

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fatal natural killer cell lymphoma arising in a patient with a crop of Epstein-Barrvirus-associated disorders.2005

    • Author(s)
      Nitta Y, Kojima S, et al.
    • Journal Title

      Eur J Dermatol. 15(6)

      Pages: 503-506

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Features and outcome of neonatal leukemia in Japan : Experience of the Japan Infant Leukemia Study Group.2005

    • Author(s)
      Ishii E, Kojima S, et al.
    • Journal Title

      Pediatr Blood Cancer. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aplastic anemia.2005

    • Author(s)
      Kojima S, Frickhofen, et al.
    • Journal Title

      Int J Hematol. 82

      Pages: 408-411

    • NAID

      10016916920

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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