1995 Fiscal Year Final Research Report Summary
Study of Leukemogenesis in Adult T-Cell Leukemia using SCID mouse model
| Project/Area Number |
06454210
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KOYANAGI Yoshio Tokyo Medical & Microbiology Associate Professor Dental University, 医学部, 助教授 (80215417)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yuetsu Kitasato University Immunology Associate Professor, 理学部, 助教授 (30163588)
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| Project Period (FY) |
1994 – 1995
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| Keywords | SCID mouse / ATL / HTLV-I / T cell lymphoma |
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| 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.
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[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
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