2004 Fiscal Year Final Research Report Summary
The mechanism of immune insufficiency against retroviral tumors and its restoration
| Project/Area Number |
15023217
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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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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KANNAGI Mari Tokyo Medical and Dental University, Graduate School, the Department of Immunotherapeutics, Professor, 大学院医歯薬学総合研究科, 教授 (80202034)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Retovirus / Leukemia / Cytotoxic T lymphocytes / Translational Research / Tumor immunology |
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| Research Abstract |
It has been noted that adult T-cell leukemia (ATL) is incidentally associated with mother-to-child infection, mostly established via mother milk. In our rat system, orally infected rats exhibited significantly higher levels of persistent human T-cell leukemia virus type I (HTLV-I) load and much weaker immune response to HTLV-I than that in intraperitoneally infected rats. As a result, persistent viral load was inversely correlated with levels of virus-specific T-cell responses. The insufficient immune responses in orally infected rats could be, however, recovered by subcutaneous re-immunization with appropriate antigens. We also investigated cellular immune responses of ATL patients who obtained complete remission following non-myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical sibling donors, and found that HTLV-I Tax-specific CTL response was strongly activated in some of these patients post-HSCT but not before HSCT. These findings suggest that HTLV-I-specific immune insufficiency established at primary HTLV-I infection may be an underlying risk factor for development of ATL, but could be overcome with immunological strategies.
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[Journal Article] Graft-versus-Tax response in adult T-cell leukemia patients after hematopoietic stem cell transplantation.2004
Author(s)
N.Harashima, K.Kurihara, A.Utsunomiya, R.Tanosaki, S.Hanabuchi, M.Masuda, T.Ohashi, F.Fukui, A.Hasegawa, T.Masuda, Y.Takaue, J.Okamura, M.Kannagi.
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Journal Title
Cancer Res. 64
Pages: 391-399
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Repression of Tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by Tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model.2004
Author(s)
M.Nomura, T.Ohashi, K.Nishikawa, H.Nishituji, K.Kurihara, A.Hasegawa, R.Furuta, J.Fujisawa, Y.Tanaka, S.Hanabuchi, N.Harashima, T.Masuda, M.Kannagi.
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Journal Title
J.Virol. 78
Pages: 3827-3836
Description
「研究成果報告書概要(欧文)」より
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