1996 年度実績報告書

がん免疫寛容のメカニズムとその制御

研究課題

研究課題/領域番号	06282103
研究機関	千葉大学
研究代表者	谷口克千葉大学, 医学部, 教授 (80110310)
研究分担者	西村孝司東海大学, 医学部, 助教授 (30143001) 藤原大美大阪大学, 医学部, 助教授 (70116094) 奥村康順天堂大学, 医学部, 教授 (50009700) 西村泰治熊本大学, 医学部, 教授 (10156119) 高橋利忠愛知県がんセンター研究所, 免疫学部, 副所長 (00124529)
キーワード	免疫寛容 / MHCペプチド / T細胞エピトープ / 養子免疫療法 / NKT細胞 / IL-12 / 補助シグナル
研究概要	がんに対する末梢性免疫寛容成立の機序とその制御メカニズムを検討し、以下の諸点を明らかにした。 1.P53ペプチドのT細胞エピトープを同定でき、それらを認識するCD4T細胞クローンを樹立した。 2.TL拘束性をもつCTLクローンを樹立し、TCRVBusageを検討。限られたVB鎖の使用が特徴的であった。 3.FasL遺伝子導入により好中球を主とする炎症機序により腫瘍拒絶がおこり、腫瘍免疫が誘導されることを確認した。CD86導入によりCTLの誘導が可能となった。 4.B7とIL-12遺伝子導入により寛容阻害に導き、強い抗腫瘍活性が得られた。 5.B細胞によってがん免疫低下がおこることを証明。それはCD40、CD40L相互作用阻害により、IL12、γ-IFN産生抑制による。 6.NKT細胞が肝へのがん転移を抑制する中心的な細胞であることを証明した。 7.ヒトMAGE-3のMHCペプチドによりCTLを誘導することに成功した。

研究成果

(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Taniguchi,M.,: "Essential requirement of an invariant Vα14 T cell antigen receptor expression in the development of natural killer T cells." Proc.Natl.Acad.Sci.USA. 93. 11025-11028 (1996)
[文献書誌] Makino,Y..: "Development of Vα14^+NKT cells in the early stages of embryogenesis." Proc.Natl.Acad.Sci.USA. 93. 6516-6520 (1996)
[文献書誌] Matsuoka,T.: "Altered TCR ligands affect antigen-presenting cell responses : Up-regulation of IL-12 by an analogue peptide." J.Immunol.157. 4837-4843 (1996)
[文献書誌] Murakami,S.: "Binding of Ras-or p53-derived peptides to HLA-DR molecules : possible candidates of targets for tumor specific T lymphocytes." Immunol.Lett.49. 149-153 (1996)
[文献書誌] Tsujimura,K.: "Positive selection of γδ CTL by TL antigen expressed in the thymus." J.Exp.Med.184. 2175-2184 (1996)
[文献書誌] Taguchi,O.: "Mouse models of autoimmune disease suggest that self-tolerance is maintained by autoreactive T cells in unresponsiveness and active suppressor T cells." Immunology. 89. 13-19 (1996)
[文献書誌] Doi,T.,: "NF-κB RelA deticient lymphocytes : Normal development of T-cells and B-cells,impaired production of lgA and lgG1 and reduced proliferative responses." J.Exp.Med.(in press).
[文献書誌] Yagita,H.,: "CD95 ligand in graft rejection." Nature. 379-682 (1996)
[文献書誌] Kato,K.: "Local production of IL-12 p40 suppresses Th-1-mediated immune reponses and prevents allogeneic myobast rejection." Proc.Natl.Acad.Sci.USA.93. 9085-9089 (1996)
[文献書誌] Nakano,H.,: "TRAF5,an activator of NF-κB and putative signal transducer for the lymphotoxin-β receptor." J.Biol.Chem.271. 14661-14664 (1996)
[文献書誌] Maruo,S.: "IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones." J.Immunol.156. 1748-1755 (1996)
[文献書誌] Fujiwara,H.: "The anti-tumor and anti-metastatic effects of interleukin-12." Cancer Chemother Phamacol. 38. S22-S26 (1996)
[文献書誌] Yu,W-G.: "Molecular mechanisms underlying IFN-γ-mediated tumor growth inhibition induced during tumor immunotherapy with rIL-12." Int.Immunol.8. 855-865 (1996)
[文献書誌] Fujiwara,H.: "Cellular and molecular mechanisms underlying IL-12 induced tumor regression." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY Acad.Sci.795. 294-309 (1996)
[文献書誌] Nishimura,T.: "The application of IL-12 to cytokine and gene therapy of tumor." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY. Acad.Sci.791. 375-378 (1996)
[文献書誌] Nishimura,T.: "The therapeutic effect of IL-12 or its antagonist in transplantation immunity." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY Acad.Sci.791. 371-374 (1996)
[文献書誌] Tanaka,Y.: "A pivotal role of interleukin-12 in Th1-dependent mouse live injury." Int.Immunol.8. 569-576 (1996)
[文献書誌] Eura,M.: "Expression of the MAGE gene family in human head and neck squamous cell carcinomas" Int.J.Cancer.64. 304-308 (1996)

1996 年度 実績報告書

がん免疫寛容のメカニズムとその制御

研究代表者

谷口 克 千葉大学, 医学部, 教授 (80110310)

研究成果

[文献書誌] Taniguchi,M.,: "Essential requirement of an invariant Vα14 T cell antigen receptor expression in the development of natural killer T cells." Proc.Natl.Acad.Sci.USA. 93. 11025-11028 (1996)

[文献書誌] Makino,Y..: "Development of Vα14^+NKT cells in the early stages of embryogenesis." Proc.Natl.Acad.Sci.USA. 93. 6516-6520 (1996)

[文献書誌] Matsuoka,T.: "Altered TCR ligands affect antigen-presenting cell responses : Up-regulation of IL-12 by an analogue peptide." J.Immunol.157. 4837-4843 (1996)

[文献書誌] Murakami,S.: "Binding of Ras-or p53-derived peptides to HLA-DR molecules : possible candidates of targets for tumor specific T lymphocytes." Immunol.Lett.49. 149-153 (1996)

[文献書誌] Tsujimura,K.: "Positive selection of γδ CTL by TL antigen expressed in the thymus." J.Exp.Med.184. 2175-2184 (1996)

[文献書誌] Taguchi,O.: "Mouse models of autoimmune disease suggest that self-tolerance is maintained by autoreactive T cells in unresponsiveness and active suppressor T cells." Immunology. 89. 13-19 (1996)

[文献書誌] Doi,T.,: "NF-κB RelA deticient lymphocytes : Normal development of T-cells and B-cells,impaired production of lgA and lgG1 and reduced proliferative responses." J.Exp.Med.(in press).

[文献書誌] Yagita,H.,: "CD95 ligand in graft rejection." Nature. 379-682 (1996)

[文献書誌] Kato,K.: "Local production of IL-12 p40 suppresses Th-1-mediated immune reponses and prevents allogeneic myobast rejection." Proc.Natl.Acad.Sci.USA.93. 9085-9089 (1996)

[文献書誌] Nakano,H.,: "TRAF5,an activator of NF-κB and putative signal transducer for the lymphotoxin-β receptor." J.Biol.Chem.271. 14661-14664 (1996)

[文献書誌] Maruo,S.: "IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones." J.Immunol.156. 1748-1755 (1996)

[文献書誌] Fujiwara,H.: "The anti-tumor and anti-metastatic effects of interleukin-12." Cancer Chemother Phamacol. 38. S22-S26 (1996)

[文献書誌] Yu,W-G.: "Molecular mechanisms underlying IFN-γ-mediated tumor growth inhibition induced during tumor immunotherapy with rIL-12." Int.Immunol.8. 855-865 (1996)

[文献書誌] Fujiwara,H.: "Cellular and molecular mechanisms underlying IL-12 induced tumor regression." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY Acad.Sci.795. 294-309 (1996)

[文献書誌] Nishimura,T.: "The application of IL-12 to cytokine and gene therapy of tumor." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY. Acad.Sci.791. 375-378 (1996)

[文献書誌] Nishimura,T.: "The therapeutic effect of IL-12 or its antagonist in transplantation immunity." In “Interleukin-12 : Cellular and Molecular Immunology of an Important Regulatory Cytokine" Ann.NY Acad.Sci.791. 371-374 (1996)

[文献書誌] Tanaka,Y.: "A pivotal role of interleukin-12 in Th1-dependent mouse live injury." Int.Immunol.8. 569-576 (1996)

[文献書誌] Eura,M.: "Expression of the MAGE gene family in human head and neck squamous cell carcinomas" Int.J.Cancer.64. 304-308 (1996)

1996 年度実績報告書

谷口克千葉大学, 医学部, 教授 (80110310)