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戦略的基礎研究推進事業 平成７年度採択研究課題 研究終了報告  181-196
ウイルス持続感染による免疫均衡の破綻機序とその免疫治療法の開発
神奈木 真理

主な研究成果
(1)論文発表
A. 神奈木グループ(東京医科歯科大学)
1. S. Hanabuchi, T. Ohashi, Y. Koya, H. Kato, A. Hasegawa, F. Takemura, T. Masuda, M. Kannagi. Regression of HTLV-I-lymphomas by peptide-induced T-cell immunity with a newly identified Tax-epitope in rats. J. NCI, in press, 2001.
2. M. Kannagi, T. Ohashi, S. Hanabuchi, H. Kato, Y. Koya, A. Hasegawa, T. Masuda, and T. Yoshiki. Immunological aspects of rat models of HTLV-type 1-infected T lymphoproliferative disease. AIDS Res. Hum. Retroviruses 16: 1737-1740, 2000.
3. T. Ohashi, S. Hanabuchi, H. Kato, H. Tateno, F. Takemura, T. Tsukahara, Y. Koya, A. Hasegawa, T. Masuda, and M. Kannagi. Prevention of adult T cell leukemia-like lymphoproliferative disease in rats by adoptively transferred T cells from a donor immunized with human T cell leukemia virus type 1 Tax-coding DNA vaccine. J. Virol. 74: 9610-9616, 2000.
4. N. Tsurutani, M. Kubo, Y. Maeda, T. Ohashi, N. Yamamoto, M. Kannagi, T. Masuda. Identification of critical amino acid residues in human immunodeficiency virus type 1 IN required for efficient proviral DNA formation at steps prior to integration in dividing and nondividing cells. J. Virol. 74: 4795-4806, 2000.
5. S. Hanabuchi, T. Ohashi, Y. Koya, H. Kato, F. Takemura, K. Hirokawa, T. Yoshiki, H. Yagita, K. Okumura, and M. Kannagi. Development of human T cell leukemia virus type I (HTLV-I)-transformed tumor in rats following suppression of T cell immunity by CD80 and CD86 blockade. J. Virol., 74: 428-435, 2000.
6. T. Tsukahara, M. Kannagi, T. Ohashi, H. Kato, M. Arai, G. Nunez, Y. Iwanaga, N. Yamamoto, K. Ohtani, M. Nakamura, and M. Fujii. Induction of Bcl-xL expression by HTLV-I Tax through NF-kB in apoptosis-resistant T-cell transfectants with Tax. J. Virol., 73: 7981-7987, 1999.
7. T. Ohashi, S. Hanabuchi, H. Kato, Y. Koya, F. Takemura, K. Hirokawa, T. Yoshiki, Y. Tanaka, M. Fujii, and M. Kannagi. Induction of ATL-like lymphproliferative disease and its inhibition by adoptive immunotherapy in T-cell deficient nude rats inoculated with syngenic HTLV-I-immortalized cells. J. Virol. 73: 6031-6040, 1999.
8. Y. Koya, T. Ohashi, H. Kato, S. Hanabuchi, T. Tsukahara, F. Takemura, K. Etoh, M. Matsuoka, M. Fujii, and M. Kannagi. Establishment of a seronegative HTLV-I-carrier state in rats inoculated with a syngeneic HTLV-I-immortalized T cell line preferentially expressing Tax. J. Virol. 73: 6436-6443, 1999.
9. H. Iwanaga, T. Tsukahara, T. Ohashi, Y. Tanaka, M. Arai, M. Nakamura, K. Ohtani, M. Kannagi, N. Yamamoto, and M. Fujii. Human T-cell leukemia virus type 1 Tax protein abrogates interleukin-2 dependence in a mouse T-cell line. J. Virol. 73: 1271-1277, 1999.
10. N. Nakamura, M. Fujii, T. Tsukahara, M. Arai, T. Ohashi, H. Wakao, M. Kannagi, N. Yamamoto. Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells. Oncogene. 18: 2667-2675, 1999.
11. T. Ohashi, M. Kubo, H. Kato, A. Iwamoto, H. Takahashi, M. Fujii, and M. Kannagi. Role of class I major histcompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 (HIV-1) replication by CD8+ T lymphocytes. J. Gen. Virol. 80: 209-216, 1999.
12. H. Kato, Y. Koya, T. Ohashi, S. Hanabuchi, and M. Kannagi. Lack of immune responses with persistent infection in adult rats by oral administration of HTLV-I. 10th International Congress of Immunology, Monduzzi editore, International Proceedings Division, Edited by G.P. Talwar, Indira Nath, N.K. Ganguly, K.V.S. Rao, pp 1117-1121, 1998.
13. H. Kato, Y. Koya, T. Ohashi, S. Hanabuchi, F. Takemura, M. Fujii, H. Tsujimoto, A. Hasegawa, and M Kannagi. Oral administration of HTLV-I induces immune unresponsiveness with persistent infection in adult rats. J. Virol. 72:7289-7293, 1998.
14. T. Ohashi, M. Arai, H. Kato, M. Kubo, M. Fujii, N. Yamamoto, A. Iwamoto, M. Kannagi. High SDF-1 expression in HIV-1 carriers does not correlate with CD8+ T cell-mediated suppression of viral replication. Virology. 244: 467-472, 1998.
15. M. Arai, T. Ohashi, T. Tsukahara, T. Murakami, T Hori, T. Uchiyama, N. Yamamoto, M. Kannagi, M. Fujii. Human T cell leukemia virus type 1 Taxprotein induces the expression of lymphocyte chemoattractant SDF-1/PBSF. Virology. 241: 298-303, 1998.
16. M. Arai, Kannagi M., Matsuoka M., Sato T., Yamamoto N., and Fujii M. Expression of FAP-1 (Fas-associated phosphatase) and resistance to Fas-mediated apoptosis in T-cell lines derived from human T-cell leukemia virus type 1 -associated myelopathy/tropical spastic paraparesis. AIDS Res. Hum. Retroviruses, 14: 261-267, 1997.
17. M. Kubo, Ohashi T., Fujii M., Oka S., Iwamoto S., Harada S., Kannagi M. Abrogation of in vitro suppression of HIV-1 replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of TNF-a. J. Virol. 71: 7560-7566, 1997.
18. M. Kannagi, Nakamura T., Akari H., Kuroda M.J., Fujii M., Oka S., Iwamoto A.,Kurata T., Higashi D., and Harada S. Dual phasic suppression of viral replication following de novo human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes of asymptomatic HIV-1 carriers. Leukemia 11 (suppl 3): 545-547, 1997.
他2件(F-5、11と重複につき省略)
B. 山本グループ(東京医科歯科大学)
1. Mori N, Morishita M, Tsukazaki T, Giam CZ, Kumatori A, Tanaka Y, Yamamoto N. Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300. Blood. 97:2137-44. 2001
2. Miura Y, Misawa N, Maeda N, Inagaki Y, Tanaka Y, Ito M, Kayagaki N, Yamamoto N, Yagita H, Mizusawa H, Koyanagi Y. Critical Contribution of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) to Apoptosis of Human CD4(+) T Cells in HIV-1-infected hu-PBL-NOD-SCID Mice. J Exp Med. 193:651-60. 2001.
3. Mori N, Ueda A, Geleziunas R, Wada A, Hirayama T, Yoshimura T, Yamamoto, N.: Induction of monocyte chemoattractant protein-1 by helicobacter polori involves NF-kB. Infect. Immun. 69 (3): 1280-1286, 2001
4. Ryo A, Kondoh N, Wakatsuki T, Hada A, Yamamoto M, Yamamoto N: A Modified Serial analysis of gene expression that generates longer sequence tags by nonpalindromic cohesive linker ligation. Anal. Biochem. 277:160-162, 2000
5. Momoi Y, Ichiyama K, Chowdhury IH, Koyanagi Y, Yamamoto N.: Pertussis toxin enhances human immunodeficiency virus type 1 replication. AIDS Res. Hum. Retrov., 16:373-9, 2000
6. Mori N, Ueda A, Ikeda S, Yamasaki Y, Yamada Y, Tomonaga M, Morikawa S, Geleziunas R, Yoshimura T, Yamamoto N.: Human T-cell leukemia virus type I tax activates transcription of the human monocyte chemoattractant protein-1 gene through two nuclear factor-kappaB sites. Cancer Res., 60: 4939-45, 2000
7. Ryo A, Suzuki Y, Arai M, Kondoh N, Wakatsuki T, Hada A, Shuda M, Tanaka K, Sato C, Yamamoto M, Yamamoto N.: Identification and characterization of differentially expressed mRNAs in HIV type 1-infected human T cells. AIDS Res Hum Retroviruses. 16:995-1005, 2000
8. Y. Suzuki, Y. Koyanagi, Y. Tanaka, N. Murakami, T. Misawa, H, Kimura, H. Shida, J.A. Hoxie, W.A. O’ Brien and N. Yamamoto: Determinant in human immunodeficiency virus type 1 for efficient replication under Cytokine-Induced CD4 + T-helper 1 (Th1)-and Th2-Type conditions. J. Virol., 73: 316-324, 1999.
9. K. Ichiyama, H. Akimoto, L.P. Neoh, N.T. Hitokawa, H. Kanemoto, S. Hirose, Y. Kanemoto, N. Yamamoto: HIV type 2 can bind to CD8 molecules but does not infect CD8 + T Cells. AIDS Res. Hum. Retrov., 15(7), 687-688, 1999.
10. Ichiyama K, Ishikawa D, Tanaka Y, Kashiwa T, Koyanagi Y, Handa S, Yamashita A, Fukushi M, Yamamoto N, Taki T (1999) Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library : comparison with ELISA using synthetic peptide. Viral Immunology 12 57-66.
11. T. Murakami, T.Y.Zhang, Y. Koyanagi, Y. Tanaka, J. Kim. Y. Suzuki, S. Minoguchi, H. Tamamura, M. Waki, A. Matsumoto, N. Fujii, H. Shida, J.A. Hoxie, S.C. Peiper and N. Yamamoto: Inhibitory mechansim of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection. J. Virol., 73, 7489-7496, 1999
12. N. Mori, Y. Nunokawa, Y. Yamada. S. Ikeda, M. Tomonaga and N. Yamamoto: Expression of human inducible nitric oxide synthase gene in T-cell lines infected with human T-cell leukemia virus type 1 and primary adult T-cell leukemia cells. Blood, 94: 2862-2870, 1999
13. M.Fukusi, J.Dixon, T.Kimura, N.Tsurutani, M.J.dixon and N.Yamamoto: Identification and cloning of a novel cellular protein Naf1,Nef-associatedfactor1,that increases cell surface CD4expressin. FEBS Lett,441,353-356,1998.
14. Y. Zhou, S. Horiuchi, M. Yamamoto and N. Yamamoto: Elevated serum levels of the soluble form of gp130, the IL-6 signal transducer, in HTLV-1 infection and no involvement of alternative splicing for its generation. Microbiol. Immunol., 42, 109-116,1998.
15. S. Horiuchi, W. Ampofo, Y. Koyanagi, A. Yamashita, M. Waki, A. Matsumoto, M. Yamamoto, N. Yamamoto: High level production of alternatively spliced soluble interleukin-6 receptor in serum of patients with adult T cell leukemia/HTLV-I associated myelopathy. Immunol., 95, 360-369, 1998.
16. M. Fukushi, J. Dixon, T. Kimura, N. Tsurutani, M.J. Dixon and N. Yamamoto: Identification and cloning of a novel cellular protein Naf1, Nef-associated factor 1, that increases cell surface CD4 expression. FEBS Lett., 441, 353-356, 1998.
17. N. Mori, N. Mukaida, D.W. Ballard, K. Matsushima and N. Yamamoto: Human T-cell leukemia virus type I tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kB-like sites, Cancer Res. 58,3993-4000, 1998
18. N. Mori, Y. Yamada, M. Tomonaga, S. Ikeda and N. Yamamoto: Interleukin-15 simulates the proliferation of peripheral blood leukemic cells from adult T-cell leukemia patients. Eur. J. Haematol, 61,278-279, 1998
19. H. Akimoto, H. Kaneko, I. Sekigawa, H. Hashimoto, Y. Kaneko and N. Yamamoto: Binding of HIV-2 envelope glycoprotein to CD8 molecules and related chemokine. Immunology, 95:214-218, 1998
20. Y. Koyanagi, Y. Tanaka, J. Kira, M. Ito, K. Hioki, N. Misawa, Y. Kawano, K. Yamasaki, R. Tanaka, Y. Suzuki, Y. Ueyama, E. Terada, T. Tanaka, M. Miyasaka, T. Kobayashi, Y. Kumazawa and N Yamamoto: Primary viremia and CNS invasion with HIV-1 in a novel hu-PBL-immunodeficient mouse. J. Virol., 71, 2417-2424, 1997.
21. Y. Koyanagi, Y. Tanaka, R. Tanaka, N. Misawa, Y. Kawano, T. Tanaka, M. Miyasaka, M. Ito, Y. Ueyama and N. Yamamoto: High levels of viremia in hu-PBL-NOD-scid with HIV-1 infection. Leukemia, 11, 109-112, 1997.
22. K. Horiuchi, Y. Koyanagi, Y. Tanaka, M. Waki, A. Matsumoto, W.Y. Zhou, M. Yamamoto and N. Yamamoto: Altered interleukin 2 receptor a-chain is expressed in human T-cell lymphotropic virus type-I (HTLV-I) infected T-cell lines and human peripheral blood mononuclear cells of adult T-cell leukemia (ATL) patients through an alternative splicing mechanism. Immunology, 91, 28-34, 1997.
23. T. Murakami, T. Nakajima, Y. Koyanagi, K. Tachibana, N. Fujii, H. Tamamura, N. Yoshida, M. Waki, A. Matsumoto, O. Yoshie, T. Kishimoto, N. Yamamoto and T. Nagasawa: A small molecule CXCR4 inhibitor that blocks T cell-line tropic HIV-1 infection. J. Exp. Med., 186, 1389-1393, 1997.
24. Y. Kawano, Y. Tanaka, N. Misawa, R. Tanaka, J. Kira, T. Kimura, M. Fukushi, K. Sano, T. Goto, M. Nakai, T. Kobayashi, N. Yamamoto and Y. Koyanagi: Mutation analysis of HIV-1 accessory genes: Requirement of site in nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. J. Virol., 71, 8456-8466, 1997.
他15件(A-4, 6, 9, 10, 14, 15, 16, E-1, 7, F-1, 2, 3, 4, 5, 6, 7と重複につき省略)
C. 井川グループ(東京医科歯科大学)
1. T. Kojima, Y. Ikawa, and I. Katoh. Analysis of molecular interactions of the p53 family p51(p63) gene products in a yeast two-hybrid system: homotypic and heterotypic interactions and association with p53-regulatory factors, Biochem. Biophys. Res. Commmun. 281 1170-1175, 2001
2. Shinohara, H., Yagita, H., Ikawa, Y., and Oyaizu, N. : Fas drives cell cycle progression in glioma cells via extracellular signal regulated kinase (ERK1/2) activation. Cancer Res. 60:1766-1772, 2000
3. I. Katoh, K. Aisaki, S. Kurata, S. Ikawa, and Y. Ikawa. p51A(TAp63gamma), a p53 homolog, accumulates in response to DNA damage for cell regulation. Oncogene 19 3126-3130, 2000
4. T. Matsuzaki, K. Aisaki, Y. Yamamura, M. Noda, and Y. Ikawa. Induction of erythroid differentiation by inhibition of Ras/ERK pathway in a Friend Murine leukemia cell line, Oncogene 19 1500-1508, 2000
5. S. Ikawa, A. Nakagawara, and Y. Ikawa. p53 family genes: structural comparison, expression and mutation, Cell Death Differ. 6 1154-1161, 1999
6. M. Sunahara, T. Shishikura, M. Takahashi, S. Todo, N. Yamamoto, H. Kimura, S. Kato, C. Ishioka, S. Ikawa, Y. Ikawa, and A. Nakagawara. Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer, Oncogene 18 3761-3765, 1999
7. Shimada, S. Kato, K. Enjo, M. Osada, Y. Ikawa, K. Kohno, M. Obinata, R. Kanamaru, S. Ikawa, and C. Ishioka. The transcriptional activities of p53 and its homologue p51/p63: similarities and differences, Cancer Res. 59 2781-2786, 1999
8. S. Ikawa, M. Obinata, and Y. Ikawa. Human p53-p51(p53-related) fusion protein: a potent BAX transactivator, Jpn. J. Cancer. Res. 90 596-599, 1999
9. H. Anzai, M. Nagayoshi, M. Obata, Y. Ikawa, and T. Atsumi. Self-renewal and differentiation of a basic fibroblast growth factor-dependent multipotent hamatopoietic cell line derived from embryonic stem cells, Dev. Growth Differ. 41 51-58, 1999
10. K. Aisaki, H. Kanno, N. Oyaizu, Y. Hara, S. Miwa, and Y. Ikawa. Apoptotic changes precede mitochondrial dysfuction in red cell-type pyruvate kinase mutant muse erythroleukemia cell lines, Jpn. J. Cancer Res. 90 171-179, 1999
11. M. Osada, M. Ohba, C. Kawahara, C. Ishioka, R. Kanamaru, I. Katoh, Y. Ikawa, Y. Nimura, A. Nakagawara, M. Obinata, and S. Ikawa. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat. Med. 4 839-843, 1998
12. S. Tajima, W.Z. Zhuang, M.V. Kato, K. Okada, Y. Ikawa, and Y. Aida. Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma, Virology 243 235-246, 1998
13. Y. Yamamura, H. Senda, Y. Kageyama, T. Matsuzaki, M. Noda, and Y. Ikawa. Erythropoietin and Friend virus gp55 activate different JAK/STAT pathways through the erythropoietin receptor in erythroid cells, Mol. Cell Biol. 18 1172-1180, 1998
14. M.V. Kato, H. Sato, M. Nagayoshi, and Y. Ikawa. Upregulation of the elongation factor-1a gene by p53 in association with death of an erythroleukemic cell line, Blood 90 1373-1378, 1998
15. Y. Ikawa. Pathogenesis of Friend leukemia virus, Leukemia Suppl. 3 152-154, 1997
16. H. Amanuma, T. Yugawa, N. Watanabe, and Y. Ikawa. Mutational analysis of the structure-function relationship of the leukemogenic membrane glycoprotein (GP55) of Friend spleen focus-forming virus (F-SFFV), Leukemia Suppl. 3 160-161, 1997
17. W. Zhuang, S. Tajima, K. Okada, Y. Ikawa, and Y. Aida. Point mutation of p53 tumor suppressor gene in bovine leukemia virus-induced lymphosarcoma, Leukemia Suppl. 3 344-346, 1997.
18. M.V. Kato, H. Sato, H. Anzai, M. Nagayoshi, and Y. Ikawa. Up-regulation of cell cycle-associated genes by p53 in apoptosis of an erythroleukemic cell line, Leukemia Suppl. 3 389-392, 1997.
19. Y. Yamamura, H. Senda, M. Noda, and Y. Ikawa. Activation of the JAK1/STAT5 pathway by binding of the Friend virus gp55 glycoprotein to the erythropoietin receptor, Leukemia suppl. 3 342-344, 1997
D. 中村グループ(東京医科歯科大学)
1. Huang, Y-P., Ohtani, K., Matsumura, Y. & Nakamura, M. Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax of human T-cell leukemia virus type I. Oncogene., 20, 1094-1102, 2001.
2. Iwanaga, R., Ohtani, K., Hayashi, T., Kumamoto, Y. & Nakamura, M. Molecular mechanisms of cell cycle progression induced by the oncoprotein Tax of human T-cell leukemia virus type I. Oncogene., , in press, 2001.
3. Ohtani, K., Iwanaga, R., Arai, M., Huang, Y-P., Matsumura, Y. & Nakamura, M. Cell type-specific E2F activation and cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I. J. Biol. Chem., 275, 11154-11163, 2000.
4. Iwanaga, R., Ohtani, K. & Nakamura, M. Requirement of cell growth for gene expression induced by the lactose and tetracycline repressor-operator combination system in a human T cell. Biochem. Biophys. Res. Commun., 276, 546-552, 2000.
5. Higashimura, N., Takasawa, N., Tanaka, Y., Nakamura, M. & Sugamura, K. Induction of OX40, a receptor of gp34, on T cells by trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I. Jpn. J. Cancer Res., 87, 227-231, 1996.
6. Ohtani, K., Iwanaga, R., Nakamura, M., Ikeda, M., Yubata, N., Tsuruga, H. & Nojima, H. Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. Oncogene, 18, 2299-2309, 1999.
7. Ohtani, K., Tsujimoto, A., Tsukahara, T., Numata, N., Miura, S., Sugamura, K. & Nakamura, M. Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I. J. Biol. Chem., 273, 14119-14129, 1998.
8. Ohtani, K., Tsujimoto, A., Ikeda, M. & Nakamura, M. Regulation of cell growth-dependent expression of mammalian CDC6 gene by cell cycle transcription factor E2F. Oncogene, 17, 1777-1785, 1998.
9. Nakamura, M., Takasawa, N., Ohbo, K., Higashimura, N., Ohtani, K., Tanaka, Y. & Sugamura, K. HTLV-I Tax trans-activation and cell growth signaling. Leukemia, 11, 7-9, 1997.
他3件(A-6, 9, E-1と重複につき省略)
E. 田中グループ(琉球大学)
1. Takahashi Y, Tanaka Y, Yamashita A, Koyanagi Y, Nakamura M, and Yamamoto N: OX40 Stimulation by gp34/OX40 Ligand Enhances Productive HIV-1 Infection1. I. Virol., in press.
2. Hanon E, Stinchcombe J, Asquith R E, Taylor G P, Tanaka Y, Weber J N, Griffiths G M, Bangham C R M. Fratricide among CD8+ T lymphocytes naturally infected with Human T-cell lymphotropic virus type I. Immunity 13:657-664, 2000.
3. Morimoto S, Kanno Y, Tanaka Y, Takano Y, Hashimoto H, Jacquot S, Marimoto C, Schlossman F. S, Yagita H, Okumura K, Kobata T. CD134L engagement enhances human B cell Ig production: CD154/CD40, CD70/CD27, and CD134/CD134L interractions coordinately regulate T cell-dependent B cell responses. J. Immunol. 164:4097-4104, 2000.
4. Ohshima Y, Yang Liang-Peng, Uchiyama T, Tanaka Y, Baum P, Sergerie M, Hermann P, Delespesse G. OX40 costimulation enhances IL-4 expression at priming and promotes the differentiation of naive human CD4+ T cells into highIL-4-producing effectors. Blood 92:3338-3345, 1998.
5. Ohshima Y, Tanaka Y, Tozawa H, Takahashi Y, Maliszewski C, and Delespesse G. Expression and function of OX40 ligand on human dendritic cells. J. Immunol. 159:3838-3848,1997
6. Imura A, Hori T, Imada K, Kawamata S, Tanaka Y, Imamura S, and Uchiyama T. OX40 expressed on fresh leukemic cells from adult T-cell leukemia patients mediates cell adhesion to vascular endothelial cells : implication for the possible involvement of OX40 in leukemic cell infiltration. Blood 89:2951-2958,1997.
7. Tanaka Y, Koyanagi Y, Tanaka R, Kumazawa Y, Nishimura T, and Yamamoto N. Productive and lytic infection of human CD4+ type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1. J. Virol. 71:465-470,1997.
他14件(A-7, 9, B-1, 2, 8, 10, 11, 20, 21, 22, 24, D-5, 9, F-4と重複につき省略)
F. 藤井グループ(新潟大学)
1. Mori N., Fujii M., Cheng G., Ikeda S., Yamasaki Y., Yamada Y., Tomonaga M., Yamamoto N. Human T-Cell Leukemia Virus Type I Tax Protein Induces the Expression of Anti-apoptotic Gene bcl-xL in Human T-Cells through Nuclear Factor-kB and c-AMP Responsive Element Binding Protein Pathways. Virus genes, (in press)
2. Iwai K., Mori N., Oie M., Yamamoto N., Fujii M. Human T-cell Leukemia Virus Type 1 Tax Protein Activates Transcription through AP-1-Site by Inducing DNA Binding Activity in T-cells. Virology, 279, 38-46 (2001)
3. Mori N., Fujii M., Yamamoto N. Aberration in signal transduction pathway in human T-cell leukemia virus type I-infected T cells. Acta Medica Nagasakiensia, 45, 1-8 (2000)
4. Mori N., Fujii M., Iwai K., Ikeda S., Yamasaki Y., Hata T., Yamada Y., Tanaka Y., Tomonaga M., Yamamoto N. Constitutive activation of transcription factor AP-1 in primary adult T-cell leukemia cells. Blood, 95, 3915-3921 (2000)
5. Fujii M., Iwai K., Oie M., Fukushi M., Yamamoto N., Kannagi M., Mori N. Activation of oncogenic transcription factor AP-1 in T-cells infected with Human T-cell Leukemia Virus Type 1. AIDS.Res.Hum.Retro., 16, 1603-1606 (2000)
6. Mori N., Fujii M., Ikeda S., Yamada Y., Tomonaga M., Ballard D., Yamamoto N. Constitutive activation of NF-kB in primary adult T-cell leukemia cells. Blood, 93, 2360-2368 (1999)
7. Mori N., Yamamoto N., Fujii M. Activation of Nuclear Factor kappa B transcription factor by human T-cell leukemia virus type I. Acta Med.Biol., 47, 85-96 (1999)
8. Santiago F., Clark E., Chong S., Molina C., Mozafari F., Mahieux R., Fujii M., Azimi N., Kashanchi F. Transcriptional Up-Regulation of the Cyclin D2 Gene and Acquisition of New Cyclin-Dependent Kinase Partners in Human T-Cell Leukemia Virus Type 1-Infected Cells. J Virol, 73, 9917-9927 (1999)
9. Matsumoto K., Shibata H., Fujisawa J.I., Inoue H., Hakura A., Tsukahara T., Fujii M. Human T-cell leukemia virus type 1 Tax protein transforms rat fibroblasts via two distinct pathways. J Virol, 71, 4445-4451 (1997)
10. Fujii M., Minamino T., Nomura M., Miyamoto K., Tanaka J., Seiki M. v-Rel activates the proto-oncogene c-jun promoter: a correlation with its transforming activity. Leukemia, 11, 402-404 (1997)
11. S. Kishi, Saijo S.,Arai M., Karasawa S., Ueda S., Kannagi M., Iwakura Y., Fujii M., and Yonehara S. Resistance to Fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus type I (HTLV-I) transgenic mice with autoimmune arthropathy. J. Exp. Med. 186: 57-64, 1997.
他11件(A-7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18と重複につき省略)
G. 高橋グループ(日本医科大学)
1. Takahashi, M., Nakagawa, Y., Berzofsky, J.A., Takahashi, H.: Counter-regulation of cytolytic activity and cytokine production in human immunodeficiency virus (HIV)-1-specific murine CD8+ cytotoxic T lymphocytes by free antigenic peptide. Int. Immunol., 13: 43-51, 2001. (January)
2. Nakagawa, Y., Takeshita, T., Berzofsky, J.A., Takahashi, H.: Analysis of the mechanism for extracellular processing in the presentation of human immunodeficiency virus-1 envelope protein-derived peptide to epitope-specific cytotoxic T lymphocytes. Immunology, 101: 76-82, 2000.
3. Akahata, W., Ido, E., Shimada, T., Katsuyama, K., Yamamoto, H., Uesaka, H., Ui, M., Kuwata, T., Takahashi, H., Hayami, M.: DNA vaccination of macaques by a full genome HIV-1 plasmid which produces non-infections virus particles. Virol., 275: 116-124, 2000.
4. Chiaba, M., Takahashi, H., Kato, K., Nakagawa, Y., Fukushima, T., Iinuma, H., Nerome, K.: Recombinant vaccinia virus expressing an immunodominant epitope of HIV-1 envelope protein within an influenza hemagglutinin cassette predominantly prime epitope-specific CD8+ CTL. Arch. Virol., 144: 1469-1485, 1999.
5. Kmieciak, D., Wasik, T.J., Teppler, H., Pientka, J., Hus, S., Takahashi, H., Okumura, K., Kaneko, Y., and Kozbor, D.: The effect of deletion of the V3 loop of gp120 on cytotoxic T cell responses and HIV gp120-mediated pathogenesis. J. Immunol., 160: 5676-5683, 1998.
6. Sung-Tae, Y., Abe, E., Okada, Y., Matsuura, Y., Takebe, Y., Ogasawara, K., Takahashi, H., and Mizuochi, T.: A polypeptide encoded within the murine AIDS defective virusstimulates primary proliferation of CD8+ T cells. Immunol. Lett., 55: 93-98, 1997.
7. Takahashi, H., Nakagawa, Y., Leggatt, G., Ishida, Y., Saito, T., Yokomuro, K., and Berzofsky, J.A.: Inactivation of HIV-1 envelope-specific CD8+ cytotoxic T lymphocytes by free antigenic peptide: A self-veto mechanism? J. Exp. Med., 183: 879-889, 1996.
8. Shirai, M., Kurokouchi, K., Pendleton, C.D., Boyd, L.F., Takahashi, H., Margulies,D., and Berzofsky, J.: Reciprocal CTL cross-reactivity interactions between two major epitopes with HIV-1 gp160. J. Immunol., 157: 4399-4411, 1996.
他1件(A11と重複につき省略)
(2)口頭発表:(国内 170件以上, 海外60件以上)
1) 招待、口頭講演(抜粋)
1. M. Kannagi, S. Hanabuchi, T. Ohashi, A. Hasegawa, and T. Masuda. Host defense mechanisms against HTLV-I-induced T-cell lymphomas in a rat model. 10th International Conference on Human Retrovirology: HTLV and Related Viruses. June 25-29, 2001, Dublin, Ireland.
2. Takashi Ohashi, Shino Hanabuchi, Takao Masuda, and Mari Kannagi. Suppressive effects of HTLV-I Tax-coding vaccine on the development of ATL-like lymphoproliferative disease in a rat model. 12th International Workshop on Retroviral Pathogenesis, October 29 - November 1, 2000, Maryland, USA.
3. M. Kannagi, T. Ohashi, S. Hanabuchi, H. Kato, Y. Koya, and T. Yoshiki. Induction of HTLV-I-infected T-lymphoproliferative disease in animal models and its immunological aspects. Workshop on HTLV Molecular Biology and Pathogenesis, March 17-19, 2000, Virginia, U.S.A.
4. M. Fujii. Interleukin 2 independent growth induced by human T cell leukemia virus type 1 Tax protein in a mouse T cell line. Workshop on HTLV-IMolecular Biology and Pathogenesis, March 17-19, 2000, Virginia, U.S.A.
5. Takahashi, H., Norose, Y., Nakagawa, Y., Takahashi, M., Sakaguchi, M.,Takebe, Y.: Efficient priming of HIV-specific CD8+CTL with dendritic cells presensitized withHIV-DNA plasmid. Japan-US Cooperative Medical Science Program: The 12th Joint Scientific Meeting of AIDS.March 22-24, 2000 (SantaFe, New Mexico, U.S.A.)
6. T. Masuda, N. Tsurutani, N. Yamamoto, and M. Kannagi. Critical amino acid residue in HIV-1 IN required for efficient proviral formation in monocyte-derived macrophage: implication for nuclear transport function of IN, May, 1999, Cold spring Harbor.
7. M. Kannagi, T. Ohashi, S. Hanabuchi, Y. Koya, H. Kato, F. Takemura, K. Hirokawa, and T. Yoshiki. T-cell control of tumor cells in vivo in a rat model system of ATL. Ninth International Conference of Human Retrovirology HTLV and Related Viruses, April, 1999, Kagoshima.
8. M. Fujii. Critical involvement of human T-cell leukemia virus type 1 Tax protein in IL-2-independent transformation of T cells. Ninth International Conference of Human Retrovirology HTLV and Related Viruses, April, 1999, Kagoshima.
9. M. Kannagi. Host defense mechanisms against human T cell leukemia virus type I (HTLV-I). 11th International Conference of Women Engineers and Scientists. Makuhari, Chiba, July, 1999.
10. Tanaka, Y., Tanaka, R., Kumazawa, Y., Koyanagi, Y. and Yamamoto, N. Control of HIV-1 proliferation and pathogenesis with host factors in the hu-PBL-SCID mouse system. 12th World AIDS Conference, Geneva 1998/06/30
11. Kato, H., Koya, T., Ohashi, T., Hababuchi, S. and Kannagi, M. Lack of immune responses with persistent infection in adult rats by oral administration of HTLV-I. 10th International Congress of Immunology New Delhi India 1998/11/02
12. Kannagi M., et al. Roles of the MHC-I-resrtricted and unrestricted CD8+ T cell-mediated suppression of HIV-1 replication. 3rd. International Kyoto Life Science Symposum. (Kyoto) May, 1997.
13. 神奈木真理. ATLの動物モデルと腫瘍ワクチン. 日本癌学会シンポジウム、京都、2001年4月。
14. 神奈木真理. ヒトレトロウイルス腫瘍の発症と防御. 科学技術振興事業団公開シンポジウム。東京、2001 1月。
15. 神奈木真理. HTLV-Iリンパ腫瘍と免疫. 日本癌学会シンポジウム、「感染症と発癌」京都、1999、12月.
16. 中村正孝. HTLV-I Taxによる細胞増殖制御. 日本癌学会シンポジウム、「感染症と発癌」京都、1999、12月.
2) ポスター発表 (抜粋)
1. M. Kannagi, S. Hanabuchi, T. Ohashi. In vivo control of HTLV-I-infected tumor development by T cell immunity in a rat model. 11th International Congress of Virology, Sidney, Australia, August, 1999.
2. Nakamura M, Iwanaga R, Huang Y, Ohtani K. Induction of S phase of the cell cycle in human T cells by HTLV-I Tax. XIth International Congress of Virology, Sydney, Australia, 1999.
(3)特許出願
1. 大橋 貴·神奈木真理、
成人T細胞白血病モデル動物
平成10年11月5日 出願
1999年11月5日 国際出願
2. 増田貴夫·神奈木真理、
インテグラーゼN末端領域に結合する因子を標的としたHIV阻害剤スクリーニング法
平成11年5月13日 出願
2000年4月25日 国際出願
(4)受賞等
1) 受賞:研究代表者は2001年6月にダブリンで開催された第10回国際ヒトレトロウィルス学会で「ATLの動物モデルと宿主免疫」について招待講演し、Arwind Diwan賞を受賞した。
2) 新聞報道:2001年4月6-7日に京都で開催したシンポジウム「ATLのウイルス病因発見から20年」に対する共同通信の取材記事で、本研究成果(ATLの動物モデルと腫瘍ワクチン効果)が取り上げられた。
(5)その他特記事項
神奈木グループのATLに対する腫瘍ワクチンの研究は、科学技術振興事業団の平成12年度「権利化試験課題」に採用された(平成14年3月まで)。