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Study of Leukemogenesis in Adult T-Cell Leukemia using SCID mouse model

Research Project

Project/Area Number 06454210
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KOYANAGI Yoshio  Tokyo Medical & Microbiology Associate Professor Dental University, 医学部, 助教授 (80215417)

Co-Investigator(Kenkyū-buntansha) TANAKA Yuetsu  Kitasato University Immunology Associate Professor, 理学部, 助教授 (30163588)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsSCID mouse / ATL / HTLV-I / T cell lymphoma
Research Abstract

It is well known that HTLV-I is an oncogenic type C retrovirus for one of the T cell malignancies, adult T-cell leukemia (ATL). HTLV-I is a first human retrovirus which causes the human malignant tumor. Our experiment has been designed to investigate mechanism of leukemogenesis and develop therapy strategy against the ATL using an animal model.
In addition of scid mice which have an autosomal recessive mutation of the rearrangement on immunoglobulin and T-cell receptor genes resulting that they lack functional T and B lymphocytes, new immunodeficient mice were developed by either backcrossing of scid mutant onto the other mutant mice. Human T lymphocytes were reconstituted in the new immunodeficient mouse strains. Using the immunodeficient mice we developed the infection system of HTLV-I and the mice were killed by human T-cell lymphoma.
The human T-cell lymphoma in the immunodeficient mice was very similar to ATL leukemic cells and we detected active cytokine gene expression such as IL-2, IL-10, IFN-gamma, and M-CSF.Although all tumor cells contained entire HTLV-I sequence, the expression of tax gene was low. This results may implicate that tax gene is required in development of ATL cells and is not essential to maintain the proliferation of the ATL cells in vivo. It is necessary to reveal what kind of factors involve in the leukemogenesis in vivo using the immunodeficient mice.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] J.Suzuki,et al.: "The association of antibodies against HTLV-1 pX-gene mutant products with HTLV-1-associated myelopathy(HAM)/spastic pararesis(TSP)." Journal of Infectious Diseases. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Koyanagi,et al.: "High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection." Comp.Leuk.Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Hirota,et al.: "Mutational analysis of the 5′ noncoding region of human immunodeficiency virus type 1 genome." Comp.Leuk.Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.M.-Kurosaki,Y.Koyanagi,et al.: "Inhibition of HTLV-I induction and virus-induced syncytia formation by oligodeoxynucleotides." Virus Genes. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Koyanagi,et al.: "Preferential replication of HIV-1 in lymphoid organs in scid-hu-PBL mouse." Cold Spring harbor Laboratory.12. (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Tanaka,et al.: "Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization" Journal of Virology. 68. 6323-6331 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 河野祐治,小柳義夫: "医学のあゆみ-免疫疾患(中枢神経系のHIV感染)" 医学書院, 4 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 1) J.Suzuki, J.Kira, E.Baba, M.Nakamura, Y.Koyanagi, T.Nakamura, Y.Kawano, K.Yamasaki, S.Shirabe, H.Sasaki, K.Hayashi, N.Yamamoto and T.Kobayashi: "The association of antibodies against HTLV-1 pX-gene mutant products with HTLV-1-associated myelopathy (HAM) /spastic pararesis (TSP)." Journal of Infectious Diseases. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 2) Y.Koyanagi, Y.Tanaka, R.Tanaka, N.Misawa, Y.Kawano, T.Tanaka, M.Miyasaka, M.Ito, Y.Ueyama, N.Yamamoto: "High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection." Comparative Leukemia Reserach. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Hirota, Y.Koyanagi, D.-S.An, Y.Iwanaga, N.Yamamoto, K.Shimotohno: "Mutational analysis of the 5' noncoding region of human immunodeficiency virus type 1 genome." Comparative Leukemia Reserach. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 4) N.M.-Kurosaki, Y.Koyanagi, M.Mizuuchi, S.Ohki, K.Makino, N.Yamamoto: "Inhibition of HTLV-I induction and virus-induced syncytia formation by oligodeoxynucleotides" Virus Genes. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 5) Y.Koyanagi, Y.Tanaka, R.Tanaka, D.-S.An, N.Misawa, N.Yamamoto: "Preferential replication of HIV-1 in lymphoid organs in scid-hu-PBL mouse" Cold Spring harbor Laboratory. 12. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 6) Y.Tanaka, R.Tanaka, E.Terada, Y.Koyanagi, K.N.Miyano, N.Yamamoto, E.Baba, M.Nakamura, H.Shida: "Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization." Journal Virology. 68. 6323-6331 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Suzuki,et al.: "The association of antibodies against HTLV-1 pX-gene mutant products with HTLV-1-associated myelopathy(HAM)/spastic pararesis(TSP)." Journal of Infectious Diseases. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Koyanagi,et al.: "High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection." Comp.Leuk.Res.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Hirota.et al.: "Mutational analysis of the 5'noncoding region of human immunodeficiency virus type 1 genome." Comp.Leuk.Res.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] N.M.-Kurosaki,Y.Koyanagy,et al.: "Inhibition of HTLV-I induction and virus-induced syncytia formation by oligodeoxynucleotides." Virus Genes. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Koyanagi,et al.: "Preferential replication of HIV-1 in lymphoid orgens in scid-hu-PBL mouse." Cold Spring harbor Laboratory.12. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Tanaka,et al.: "Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization" Journal of Virology. 68. 6323-6331 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 河野祐治,小柳義夫: "医学のあゆみ-免疫疾患(中枢神経系のHIV感染)" 医学書院, 4 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koyanagi Y: "In vivo infection of human T-cell virus type I in non-T cells." Virology. 196. 25-33 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Koyanagi Y: "Dual infection of HIV-1 and HTLV-I in South India : A study on a patient with AIDS-related complex." Microbiol Immunol. 37. 983-986 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kira J,Koyanagi Y: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system tissue of patients with HTLV-1-associated myelopathy : Presence of pX-defective mutants" Ann Neurol. 36. 149-156 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamashita A,Yamamoto N: "Cell type-specific heterogeneity of the HIV-1 V3 loop in infected indicifuals : Selection of virus in macrophages and plasma." Virology. 204. 170-179 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka Y: "Induction of antibody responses that neutralize human T-cell leukemia virus type-1 (HTLV-1) infection in vitro and in vivo by peptide immunization : Epitope vaccine against HTLV-1" J Virol. 68. 6323-6331 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Horiuchi S: "Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are genetated through alternative splicing mechanism." Eur J Immunol. 24. 1945-4948 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 小柳 義夫: "臨床分子生物学" 日本臨床, 763-766 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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