免疫制御・寛容の分子機構

• 研究課題/領域番号: 05272103
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 九州大学
• 研究代表者: 笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)
• 研究分担者: 谷口 維紹 東京大学, 医学部, 教授 (50133616) ; 渡邊 武 (渡辺 武) 九州大学, 生体防御医学研究所, 教授 (40028684) ; 岸本 忠三 大阪大学, 医学部, 教授 (10093402) ; 本庶 佑 京都大学, 医学部, 教授 (80090504) ; 奥村 康 順天堂大学, 医学部, 教授 (50009700) ; 平野 俊夫 大阪大学, 医学部, 教授 (40136718) ; 多田 富雄 東京大学, 医学部, 教授 (10009136)
• 研究期間 (年度): 1993 – 1995
• 研究課題ステータス: 完了 (1996年度)
• 配分額: 51,000千円 (直接経費: 51,000千円); 1996年度: 3,000千円 (直接経費: 3,000千円); 1995年度: 18,000千円 (直接経費: 18,000千円); 1994年度: 13,800千円 (直接経費: 13,800千円); 1993年度: 16,200千円 (直接経費: 16,200千円)
• キーワード: 免疫制御 / 免疫寛容 / 総括班 / 情報提供 / 情報交換 / 国際シンポジウム / トランスジェニックマウス / ジーンノックアウトマウス / 免疫応答

研究概要

重点領域研究「免疫制御・寛容の分子機構」は、1)免疫制御の分子機構、2)免疫寛容の分子機構、3)免疫病の分子機構の三つの計画班と若干の公募研究で遂行され、HLA/抗原ペプチド複合体のTCRによる認識とそれによりもたらされるサイトカインの発現を中心にした免疫制御系の分子レベルでの解明、免疫疾患の発生と病態に関する遺伝子レベルからの解明、さらに個体から臓器、細胞内のシグナル伝達機構の広きに亘る病因の解明が進んだ。また、本重点領域研究では、IL-2受容体γ鎖変異マウス、CD3ξ欠損マウス、TCR-Tgマウス、Lynキナーゼ欠損マウス、HS1欠損マウスなど多くのトランスジェニックマウス、ジーンノックアウトマウスの作成がなされ、これらのマウスを利用することで研究の発展に寄与したことも特記すべきことである。総括班では、合同シンポジウム、ワークショップ、国際シンポジウムを開催し、またニュースレターを発行し、班員相互の連絡を密にし、これらの多岐にわたる研究分担課題および多数の班員の理解と協力態勢を確立すると同時に研究成果をとりまとめ公開した。

研究成果

• [文献書誌] Hori, T., et al.: "Japanese cedar pollinosis and HLA-DP5." Tissue Antigens. (in press). (1996)
• [文献書誌] Min, W., et al.: "Identification of an Epitope for T cells Correlated with Antibody Response to Hepatitis B Surface Antigen in Vaccinated Humans." Human Immunol.(in press). (1996)
• [文献書誌] Sudo, T., et al.: "Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes." J. Immunol.155. 4749-4756 (1995)
• [文献書誌] Mineta, M., et al.: "Contribution of HLA class I and Class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans." International Immunology. (in press). (1995)
• [文献書誌] Nishizumi, H., et al.: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice." Immunity. 3. 549-560 (1995)
• [文献書誌] Taniuchi, I., et al.: "Antigen-receptor induced clonal expansion and delection of lymprocytes are imbaired in the mice lacking HS1 protein, a substrate of the antigen receptor coupled tyrosine kinases." EMBO J.14. 3664-3678 (1995)
• [文献書誌] Okabe T.: "cDNA cloning of a NGF1-B/nur77 related transcription factor from an apoptotic T cell line." J.Immunol.(in press).
• [文献書誌] Takeda T.: "EIA respression of IL-6-induced gene activation by blocking the assembly of IL-6 response element binding complexes." J.Immunol.(in press).
• [文献書誌] Hara H.: "Detection of human T lymphotropic Virus Type I(HTLV-1) proviral DNA and analysis of T cell receptor V CDR3 sequences in spinal cord lesions of HTLV-1 associated myelopathy Tropical spastic paraparesis." J.Exp.Med.(in press).
• [文献書誌] Rae SM.Yeung: "Human CD4-major histocompatibility complex class II (DOW6) transgenic mice in an endogenous CD4/CD8-deficient background:Reconstitution of phenotype and human restrieted function." J.Exp.Med.180. 1911-1920 (1994)
• [文献書誌] Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DO transgenic mice." J.Exp.Med.180. 165-171 (1994)
• [文献書誌] Hanabuchi S.: "Fas and its ligand in a general mechanism of T cell-mediated cytotoxity." Proc.Natl.Acad.Sci.USA. 91. 4930-4934 (1994)
• [文献書誌] Koide Y.: "Molecular analysis of the pathogenesis of autoimmune insulitis in NOD mice." Tohoku J.Exp.Med.173. 157-170 (1994)
• [文献書誌] Nakano T.: "Generation of lymphomatopoietic cells from embryonic stem cells in culture." Science. 265. 1098-1101 (1994)
• [文献書誌] Kishimoto,T.: "Cytokine signal transduction." Cell. 76. 253-262 (1994)
• [文献書誌] Akira S.: "Molecular cloning of APRF,a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp 130-mediated signaling pathway." Cell. 77. 63-71 (1994)
• [文献書誌] Kaisho T.: "EST-1,a surface molecule of bone marrow stromal cell lines that facilitates pre-B cell growth." Proc.Natl.Acad.Sci.USA. 91. 5325-5329 (1994)
• [文献書誌] Sawada M.: "cDNA cloning of a novel protein tyrosine phosphatase with homology to cytoskeletal protein 4.1 and its expression in T-lineage cells." Biochm.Biophys.Res.Commun.203. 479-484 (1994)
• [文献書誌] Tanaka N.: "Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1." Cell. 77. 829-839 (1994)
• [文献書誌] Kimura T.: "Involvement of the IRF-1 transcription factor in antiviral responses to interferones." Science. 264. 1921-1924 (1994)
• [文献書誌] Isobe M.: "Immunosuppression to cardiac allografts and soluble antigens by anti-VCAM-1 and anti-VLA-4 monoclonal antibodies." J.Immunol.153. 5810-5818 (1994)
• [文献書誌] Yoshizumi H: "Generation of a novel CD8^+ cytotoxic T lymphocyte that requires soluble factor to lyse autologous antigen-presenting cells" Eur.J.Immunol.23. 3173-3180 (1993)
• [文献書誌] Fukui Y: "Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in aguisition of T cell tolerance to self-superant gens and processed D〓〓〓〓er〓ved peptide" Eur.J.Immunol.23. 1678-1686 (1993)
• [文献書誌] Degawa M: "Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat" Carcinogenesis. 14. 1091-1094 (1993)
• [文献書誌] Inoue T: "Distinction of mouse CD8^+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms" J.Immunol.150. 2121-2128 (1993)
• [文献書誌] Kato K: "Identification of a T cell surface signal-transducing glycoprotein sgp-60,as CD48 that is a counter-receptor for mouse CD2" Eur.J.Immunol.23. 1412-1415 (1993)
• [文献書誌] Miyake S: "B1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients" J.Exp.Med.177. 863-868 (1993)
• [文献書誌] Ryu K: "Inhibition of tyrosine phosphorylation prevents IFN-gamma-induced HLA-DR molecule expression" J.Immunol.150. 1253-1262 (1993)
• [文献書誌] Tashiro K: "Signal sequence trap:a cloning strategy for secreted proteins and type I membrane proteins" Science. 261. 600-603 (1993)
• [文献書誌] Tsubata T: "B cell apoptosis induced by antigen receptor crosslinking is blocked by T cell signal through CD40" Nature. 364. 645-648 (1993)
• [文献書誌] Nishitani S: "The bcl-2 gene porduct inhibits clonal delection of self-reactive B lymphocytes in the periphery but not in the bone marrow" J.Exp.Med.178. 1247-1254 (1993)
• [文献書誌] Murakami M: "IL-6-induced homodimerization of gp 130 and associated activation of a tyrosine kinase" Science. 260. 1808-1810 (1993)
• [文献書誌] Nakajima T: "Phosphorylation at threonine 235 by a rasdependent MAP kinase cascade is essential for transcriptional activation of NF-JL6" Proc.Natl.Acad.,USA. 90. 2207-2211 (1993)
• [文献書誌] Nakajima K: "Identification of a novel interleukin 6 responsive element containing an Ets-binding site and a CRE-like site in the junB promoter" Mol.Cell.Biol.13. 3027-3041 (1993)
• [文献書誌] Yamanashi Y: "Identification of HS1 protein as a major substrates of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling" Proc.Natl.Acad.Sci.,USA. 90. 3631-3635 (1993)
• [文献書誌] Ichiki T: "Regulation of the expression of human Ce germline transcript:Identification of a novel IL-4 responsive element" J.Immunol.150. 5408-5417 (1993)
• [文献書誌] Tamai H: "Resistance to autoimmune thyroid disease is associated with HLA-DQ" J.Clin.Endocrinol.Metab.78. 94-97 (1994)
• [文献書誌] Esaki Y: "Role of human major histocompatibility comples DQ molecules in superantigenicity of Streptococcus-derived protein" Infect.Immun.62. 1228-1235 (1994)