1996 Fiscal Year Annual Research Report

がん免疫寛容のメカニズムとその制御

Research Project

Project/Area Number	06282103
Research Institution	Chiba University
Principal Investigator	谷口克千葉大学, 医学部, 教授 (80110310)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] 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)
[Publications] Makino,Y..: "Development of Vα14^+NKT cells in the early stages of embryogenesis." Proc.Natl.Acad.Sci.USA. 93. 6516-6520 (1996)
[Publications] 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)
[Publications] 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)
[Publications] Tsujimura,K.: "Positive selection of γδ CTL by TL antigen expressed in the thymus." J.Exp.Med.184. 2175-2184 (1996)
[Publications] 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)
[Publications] 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).
[Publications] Yagita,H.,: "CD95 ligand in graft rejection." Nature. 379-682 (1996)
[Publications] 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)
[Publications] Nakano,H.,: "TRAF5,an activator of NF-κB and putative signal transducer for the lymphotoxin-β receptor." J.Biol.Chem.271. 14661-14664 (1996)
[Publications] 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)
[Publications] Fujiwara,H.: "The anti-tumor and anti-metastatic effects of interleukin-12." Cancer Chemother Phamacol. 38. S22-S26 (1996)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Tanaka,Y.: "A pivotal role of interleukin-12 in Th1-dependent mouse live injury." Int.Immunol.8. 569-576 (1996)
[Publications] Eura,M.: "Expression of the MAGE gene family in human head and neck squamous cell carcinomas" Int.J.Cancer.64. 304-308 (1996)

1996 Fiscal Year Annual Research Report

がん免疫寛容のメカニズムとその制御

Principal Investigator

谷口 克 千葉大学, 医学部, 教授 (80110310)

Research Products

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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).

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

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

谷口克千葉大学, 医学部, 教授 (80110310)