2001 Fiscal Year Annual Research Report

HTLV-Iによる自己免疫性慢性関節炎発症機構の解明

Research Project

Project/Area Number	13226021
Research Institution	The University of Tokyo
Principal Investigator	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)
Co-Investigator(Kenkyū-buntansha)	宝来玲子東京大学, 医科学研究所, 助手 (20313091) 須藤カツ子東京大学, 医科学研究所, 助手 (50126091) 保田尚孝東京大学, 医科学研究所, 講師 (90323641)
Keywords	HTLV-I / トランジェニックマウス / IL-1 / IL-6 / 自己免疫疾患 / 関節リウマチ / CD40L / OX40
Research Abstract	HTLV-IはATLの原因ウイルスとして発見されたが、HAM/TSPやシェグレン症候群など免疫系の関与が考えられる他の疾患への関与も示唆されている。我々はHTLV-Iのtax遺伝子を導入したトランスジェニクマウス(HTLV-I-Tg)を作製し、このウイルスが関節リウマチによく似た慢性関節炎を引き起こすことを初めて示した。さらに、関節炎発症に自己免疫が関与していることを見いだし、HTLV-Iが自己免疫を引き起こすことを明らかにした。本研究ではHTLV-I-Tgマウスモデルを用い、免疫異常の発症機構を解明することを目的とした。HTLV-I-Tgの炎症局所でIL-1やIL-6、TNF-αといった炎症性サイトカインが亢進していることを以前に報告したが、そのサイトカインの役割を明らかにする目的で、このHTLV-I-Tgのサイトカイン遺伝子を欠損させたところ、IL-1とIL-6が発症に重要であることが明らかとなった。IL-1やIL-6を欠損させたHTLV-I-Tgマウスでは、自己抗体の産生低下が観察されると共に、自己抗原に対するT細胞の増殖性の低下が観察された。その原因を明らかにする目的で、T細胞表面上の副シグナル分子の発現を調べたところ、CD40LやOX40の発現が低下していることが明らかとなった。これらの結果から、HTLV-I-Tgマウスの関節炎発症にはサイトカインを介したT細胞の活性化が重要な役割を果たしていることが示された。

Research Products

(25 results)

All Other

All Publications (25 results)

[Publications] Takeda, K: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells"Nature Medicine. 7. 94-100 (2001)
[Publications] Fukamauchi, F: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus"Biochem. Biphys. Res. Commun. 281. 220-226 (2001)
[Publications] Seino, K: "Requirement for NKT cells in the induction of allograft tolerance"Proc. Natl. Acad. U. S.. 98. 2577-2581 (2001)
[Publications] Ishii T: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles"Genes to Cell. 6. 71-78 (2001)
[Publications] Naruse-Nakajima, C: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1"Mecha. Develop. 102. 95-105 (2001)
[Publications] Ozaki, H: "Six-4, a putative myogenin gene regulator, is not essential for mouse embryonal development"Mol. Cell. Biol. 21. 3343-3350 (2001)
[Publications] Kotani, N: "Knockout of mouse β1,4-galactosyltransferase-1 gene results in a dramatic shift of outer chain moieties of N-glycans from type 2 to type 1 chains in hepatic membrane and plasma glycoproteins"Biochem J.. 357. 827-834 (2001)
[Publications] Boutin, H.: "Role of IL-1α and IL-1β in ischaemic brain damage"J. Neuroscience. 21. 5528-5534 (2001)
[Publications] Morita, Y: "Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function"Cell Death Differ.. 8. 614-620 (2001)
[Publications] Sato, M: "Th1 cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+CTL"J Immunol.. 167. 3687-3691 (2001)
[Publications] Imaizumi, Y: "Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia"Acta Histochem. Cytochem.. 34. 357-362 (2001)
[Publications] Dal, J.H.: "Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage"Immunology. 103. 235-243 (2001)
[Publications] Norose, K: "Organ infectivity of Toxoplasma gondii in interferon-γ knockout mice"J. Parasitol. 87. 447-452 (2001)
[Publications] Yoneto, T: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection"J. Immunol.. 166. 6236-6241 (2001)
[Publications] Hayakawa, Y: "Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide"Eur J Immunol.. 31. 1720-1727 (2001)
[Publications] Shibata, S: "Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice"Gene. 271. 261-271 (2001)
[Publications] Nakae, S: "IL-1 enhances T cell-dependent antibody production through induction of CD40L and OX40 on T cells"J. Immunol.. 167. 90-97 (2001)
[Publications] Yasuda, J: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr"Virology. 285. 181-192 (2001)
[Publications] Miura, T.: "Effect of 6-Hydroxydopamine on host resistance against Listeria monocytogenes infection. Infect"Infect Immun.. 69. 7234-7241 (2001)
[Publications] Le Feuvre, R.A: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J. Biol. Chem. (2001)
[Publications] Nakae, S: "IL-1α, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity"Int. Immunol.. 13. 1471-1478 (2001)
[Publications] Kyuwa, S.: "The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-gamma deficient mice is parallel to viral replication in hepatocytes in vitro"Adv Exp Med Biol.. 494. 95-99 (2001)
[Publications] Moshkin, M.P.: "Social behavior in male mice deficient in genes for interleukin-1"Med. Immunolo.. 3. 449-457 (2001)
[Publications] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J. Gen. Virol.. 83. 141-150 (2002)
[Publications] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD40L and OX40 expression on T cells"Arth. Rheum.. 46. 533-544 (2002)

2001 Fiscal Year Annual Research Report

HTLV-Iによる自己免疫性慢性関節炎発症機構の解明

Principal Investigator

岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)

Research Products

[Publications] Takeda, K: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells"Nature Medicine. 7. 94-100 (2001)

[Publications] Fukamauchi, F: "TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus"Biochem. Biphys. Res. Commun. 281. 220-226 (2001)

[Publications] Seino, K: "Requirement for NKT cells in the induction of allograft tolerance"Proc. Natl. Acad. U. S.. 98. 2577-2581 (2001)

[Publications] Ishii T: "Projection of three subsets of olfactory neurons expressing the odorant receptor transgene and the two cognate endogenous alleles"Genes to Cell. 6. 71-78 (2001)

[Publications] Naruse-Nakajima, C: "Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1"Mecha. Develop. 102. 95-105 (2001)

[Publications] Ozaki, H: "Six-4, a putative myogenin gene regulator, is not essential for mouse embryonal development"Mol. Cell. Biol. 21. 3343-3350 (2001)

[Publications] Kotani, N: "Knockout of mouse β1,4-galactosyltransferase-1 gene results in a dramatic shift of outer chain moieties of N-glycans from type 2 to type 1 chains in hepatic membrane and plasma glycoproteins"Biochem J.. 357. 827-834 (2001)

[Publications] Boutin, H.: "Role of IL-1α and IL-1β in ischaemic brain damage"J. Neuroscience. 21. 5528-5534 (2001)

[Publications] Morita, Y: "Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function"Cell Death Differ.. 8. 614-620 (2001)

[Publications] Sato, M: "Th1 cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8(+CTL"J Immunol.. 167. 3687-3691 (2001)

[Publications] Imaizumi, Y: "Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia"Acta Histochem. Cytochem.. 34. 357-362 (2001)

[Publications] Dal, J.H.: "Glycyrrhizin enhances interleukin-12 production in peritoneal macrophage"Immunology. 103. 235-243 (2001)

[Publications] Norose, K: "Organ infectivity of Toxoplasma gondii in interferon-γ knockout mice"J. Parasitol. 87. 447-452 (2001)

[Publications] Yoneto, T: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection"J. Immunol.. 166. 6236-6241 (2001)

[Publications] Hayakawa, Y: "Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide"Eur J Immunol.. 31. 1720-1727 (2001)

[Publications] Shibata, S: "Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice"Gene. 271. 261-271 (2001)

[Publications] Nakae, S: "IL-1 enhances T cell-dependent antibody production through induction of CD40L and OX40 on T cells"J. Immunol.. 167. 90-97 (2001)

[Publications] Yasuda, J: "T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr"Virology. 285. 181-192 (2001)

[Publications] Miura, T.: "Effect of 6-Hydroxydopamine on host resistance against Listeria monocytogenes infection. Infect"Infect Immun.. 69. 7234-7241 (2001)

[Publications] Le Feuvre, R.A: "Priming of macrophages with LPS potentiates P2X7 mediated cell death via a caspase-1 dependent mechanism, independently of cytokine production"J. Biol. Chem. (2001)

[Publications] Nakae, S: "IL-1α, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity"Int. Immunol.. 13. 1471-1478 (2001)

[Publications] Kyuwa, S.: "The severity of hepatic lesion after intraperitoneal JHMV infection in IFN-gamma deficient mice is parallel to viral replication in hepatocytes in vitro"Adv Exp Med Biol.. 494. 95-99 (2001)

[Publications] Moshkin, M.P.: "Social behavior in male mice deficient in genes for interleukin-1"Med. Immunolo.. 3. 449-457 (2001)

[Publications] Yokoyama, H.: "Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene"J. Gen. Virol.. 83. 141-150 (2002)

[Publications] Saijo, S.: "Suppression of autoimmune arthritis in IL-1-deficient mice in which T cell activation is impaired due to low levels of CD40L and OX40 expression on T cells"Arth. Rheum.. 46. 533-544 (2002)

岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120)