2000 Fiscal Year Final Research Report Summary
PATHOGENETIC ROLE OF HTLV-I IN ANIMAL MODELS FOR HTLV-l-RELATED DISEASES
| Project/Area Number |
09253201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
YOSHIKI Takashi Hokkaido University, School of Medicine, Professor, 医学部, 教授 (60220612)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Masahiko Hokkaido University, School of Medicine, Research Instructor, 医学部, 助手 (80301886)
IKEDA Hitoshi Hokkaido University, School of Medicine, Lecturer, 医学部, 講師 (20232192)
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| Project Period (FY) |
1997 – 1999
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| Keywords | HTLV-I / ANIMAL MODELS / TRANSGENIC RATS / THYMOMA / COLLAGEN VASCULAR DISEASES / HAM / TSP |
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| Research Abstract |
To investigate the pathogenetic role of HTLV-I, we established three animal models for HTLV-I-related diseases and analyzed them. Results are described below.
(1) Transgenic rats with HTLV-I pX gene under cortrol of lck promoter (lck-pX rats) ;
We established 6 lines of lck-pX rats and epithelial thymomas developed in 4 of 6 lines. Positive correlation was observed between tumor occurrence in each line and levels of pX mRNA expression in their thymuses. The thymoma expressed pX mRNA at a high level and Tax protein was detected in the thymomacells. High levels of the pX mRNA expression was evident in thymic epithelial/stromal cells of lck-pX rats before developing thymoma. Bone marrow cell transfer from lck-pX rats to normal rats induced thymomas in the recipient rats. The thymomas in recipient rats expressed pX mRNA and Tax protein.
(2) Transgenic rats with HTLV-I LTR-env-pX gene (env-pX rats)
A number of collagen vascular diseases developed in env-pX rat. By reciprocal bone marrow and spl
… More
een cell transfer experiments, at least three pathogenetic roles of the transgene were indicated. Although oligoclonal T cell expansion was found in affected joints and skin lesions, common T cell clone and specific amino acid motif of TCRVβ CDR3 region were not evident in affected lesions among env-pX rats. Since arthritis in env-pX rats was easily induced by the inoculation of type II collagen, suggesting env-pX rats are states of immune hyper responsiveness. Pretreatment with spleen cells of normal rats suppressed development of all diseases in env-pX rats, including collagen-induced arthritis. Immune regulatory CD4+CD25+T cells in spleen of env-pX rats lost the temporal increment of those in a maturating period of normal spleen.
(3) HTLV-I-infected WKAH rats for a model of HAM/TSP (HAM rats) ;
Major infected cells in the spinal cords of HAM rats were micrccglia/macrophagelineage cells. Pathogenetic increment of the pX and TNF-α expression and suppression of the bcl-2 expression were observed before starting apoptosis of oligodendrocytes in spinal cords of HAM rats, but not in those of HAM resistant strains. The suppression of bcl-2 expression was specifically evident in oligodendorocytes of HAM rats, but not in microcgial cells of HAM rats. In vitro-separated oligodendrocytes from spinal cords of HAM rats were easily underwent apoptosis by addition of cytotoxic factors compared with that of HAM resistant strains and uninfected WKAH rats. Less
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Research Products
(12 results)
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[Publications] Yamazaki, H., Ikeda, H., Ishizu, A., Nakamaru, Y., Sugaya, T., Kikuchi, K., Yamada, S., Wakisaka, A., Kasai, N., Koike, T., Hatanaka, M.and Yoshiki, T.: "A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I."International Immunololgy. Vol. 9. 339-346 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamazaki, H., Kunisada, T., Ishizu, A., Ikeda, H., Miyoshi, I., Sudo, T., Hayashi, S., Yoshiki, T.: "Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I."Oncogene. Vol. 17. 2955-2960 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ohashi, T., Nanabuchi, S., Kato, H., Koya, Y., Takemura, F., Hirokawa, K., Yoshiki, T., Tanaka, Y., Fujii, M.and Kannagi, M.: "Induction of adult T-cell leukemia-like lymphoproligerative disease and its inhibition by adoptive immunotherapy in T-cell-deficient nude rats inoculated with syngeneic human T-cell leukemia virus type l-immortalized cells."Journal of Virology. Vol. 73. 6031-6040 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kasai, T., Ikeda, H., Tomaru, U., Yamashita, I., Ohya, O., Morita, K., Wakisaka, A., Matsuoka, E., Moritoyo, T., Hashimoto, K., Higuchi, I., Izumo, S., Osame, M.and Yoshiki, T.: "A rat model of human T lymphocyte virus type I (HTLV-I) infection : in situ detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-I-induced chronic progressive myeloneuropathy."Acta Neuropathologica. Vol. 97. 107-112 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hanabuchi, S., Ohashi, T., Koya, Y., Kato, H., Takemura, F., Hirokawa, K., Yoshiki, T., Yagita, H., Okumura, K.and Kannagi, M.: "Development of human T-cell leukemia virus type l-transformed tumors in rats following suppression of T-cell immunity by CD80 and CD86 blockade."Journal of Virology. Vol.74. 428-435 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Jiang, X., Ikeda, H., Tomaru, U., Morita, K., Tanaka, Y., and Yoshiki, T.: "A rat model for T lymphocyte virus type I-associated myeloneuropathy : down-regulation of bcl-2 expression and increase in sensitivity to TNF-alpha of the spinal oligodendrocytes."Journal of Neuroimmunology. (in press).
Description
「研究成果報告書概要(欧文)」より
