1997 年度実績報告書

リンパ球機能分子(LFA)を介したT細胞の分子誘導と活性化機序の解析

研究課題

研究課題/領域番号	07407068
研究機関	順天堂大学
研究代表者	奥村康順天堂大学, 医学部, 教授 (50009700)
研究分担者	加藤和則順天堂大学, 医学部, 助手 (60233780) 八木田秀雄順天堂大学, 医学部, 助教授 (30182306)
キーワード	CD80,CD86 / TNF / TNF-R / CD27 / GVHD / CD95L
研究概要	免疫反応を惹起するのに重要な数々のLFAが知られている。我々が精力的にその役割を解析している分子群はCD28/CD80,CD86をはじめとし、CD27/CD70,CD40/CD40L,CD95/CD95L等である。CD28/CD80,CD86とCTLA-4/CD80,CD86の相互作用の相違を特にCD28遺伝子ノックアウトマウスを用い、CTLA-4からT細胞への抑制的なシグナルの存在をGVHDモデルマウス実験で明らかにすることが出来た。CD40/CD40Lの影響に関しても、CD40Lのトランスフェクタントを用い、CD40Lを介して、マクロファージ等から産生されたIL-12が大きく関与をし、結果として強いNK活性が発現する事実を腫瘍拒絶の実験系で明らかにした。ヒトで知られてきたTNFレセプター分子群であるCD27/CD70の役割をマウスモデルで調べる重要性が出現したため、CD27のマウス遺伝子の単離とその分子に対するモノクローナル抗体を作製することに成功した。それらの材料を使用し、マウスのEAEモデル実験でCD27/CD70の相互作用の重要性を明らかにした。CD95L/CD95に関しては、CD95Lによる好中球集積の事実を明らかにした。人工的に発現させたCD95Lと生理的に存在するCD95Lの免疫関連炎症反応での異なった反応性を明らかにした。

研究成果

(34件)

すべてその他

すべて文献書誌 (34件)

[文献書誌] Noto,K.,et al.: "Identification and functional characterization of mouse CD29 with a mAb." Int.Immunol.7. 835-842 (1995)
[文献書誌] Lanier,L.L.,et al.: "CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation,cytokine production,and generation of CTL^1." J.Immunol.154. 97-105 (1995)
[文献書誌] Yasuda,M.,et al.: "Expression and function of fibronectin binding integrins on rat mast cells." Int.Immunol.7. 251-258 (1995)
[文献書誌] Azuma,A.,et al.: "Augmented lung adenocarcinoma cytotoxicity by the combination of a genetically modified anti-Lewis Y antibody and antibodies to complement regulatory proteins." Scand.J.Immunol.42. 202-208 (1995)
[文献書誌] Ushiyama,C.,et al.: "Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantaion." J.Immunol.154. 2687-2696 (1995)
[文献書誌] Yagita,H.,et al.: "Fas-mediated cytotoxicity-a new immunoregulatory and pathogenic function of Thl CD4 T cells." Immunological Reviews. 146. 223-239 (1995)
[文献書誌] Seino,K.,et al.: "CD86 (B70/B7-2) on endothelial cells co-stimulates allogeneic CD4^+ T cells." Int Immunol.7. 1331-1337 (1995)
[文献書誌] Tanaka,T.,et al.: "Involvement of α1 and α4 integrins in gut mucosal injury of graft-versus-host disease." Int Immunol.7. 1183-1189 (1995)
[文献書誌] Kayagaki,N.et al.: "Metalloproteinase-mediated release of human Fas ligand." J.Exp.Med.182. 1777-1783 (1995)
[文献書誌] Nakajima,A.,et al.: "Preferential dependence of autoantibody production in murine lupus on CD86 co-stimulatory molecule." Eur.J.Immunol.25. 3060-3069 (1995)
[文献書誌] Bashuda,H.,et al.: "Induction of persistent allograft tolerance in the rat by combined treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies,donor specific transfusion,and FK506." Transplantation. 6. 117-122 (1996)
[文献書誌] Yonezawa,I.,et al.: "VLA-5 mediated interaction with fibronectin induces cytokine production by human chondrocytes." Biochem.Biophys.Res.Commur.219. 261-264 (1996)
[文献書誌] Yagita,H.,et al.: "CD95 ligand in graft rejection." Nature.379. 682 (1996)
[文献書誌] Kato,K.,et al.: "Local production of IL-12 p40 suppresses Th1-mediated immune responses and prevents allogeneic myoblast rejection." Proc.Natl.Acad.Sci.USA.93. 9085-9089 (1996)
[文献書誌] Bashuda,H.,et al.: "Specific acceptance of cardiac allografts after treatment with antibodies to CD80 and CD86 in mice." Transplantaion.28. 1039-1041 (1996)
[文献書誌] Nuriya,S.,et al.: "The differential role of CD86 and CD80 costimulatory molecules in the induction and the effector phases of contact hypersensitivity." Int.Immunol.8. 917-926 (1996)
[文献書誌] Nakano,H.,et al.: "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] Hamamura,K.,et al.: "A critical role of VLA-4 in erythropoiesis in vivo." Blood. 6. 2513-2517 (1996)
[文献書誌] Seino,K.,et al.: "Contribution of Fas ligand to cardiac allograft rejection." Int.Immunol.8. 1347-1354 (1996)
[文献書誌] Takazawa,K.,et al.: "Synergistic effects of mycophenolate Mofetil (MMF,RS-61443) and anti-LFA-1/monoclonal antibodies on the prolongation of heart allograft survival in rats." Transplantation. 28. 1980-1981 (1996)
[文献書誌] Sekine,C.,et al.: "Fas-mediated stimulation induces IL-8 secretion by rheumatoid arthritis synoviocytes independently of CPP32-mediated apoptosis." Biochem.Biophys.Res.Commun.228. 14-20 (1996)
[文献書誌] Saito,K.,et al.: "Effect of CD80 and CD86 blockade and anti-interleukin-12 treatment on mouse acute graft-vesus-host disease." Eur.J.Immunol.26. 3098-3106 (1996)
[文献書誌] Kaneko,H.,et al.: "Preferential elimination of CD28^+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis." Clin.Exp.Immunol.106. 218-229 (1996)
[文献書誌] Kaneko,Y.,et al.: "CD40-mediated stimulation of B1 and B2 cells : Implication in autoantibody production in murine lupus." Eur.J.Immunol.26. 3061-3065 (1996)
[文献書誌] Bashuda,H.,et al.: "Lack of cognate help by CD4^+ T cells and anergy of CD8^+ T cells are the principal mechanisms for anti-leukocyte function-associated antigen-l/intercellular adhesion molecule-l-induced cardiac allograft tolerance." Transplantation. 63. 113-118 (1997)
[文献書誌] Nakajima,A.,et al.: "Roles of IL^^--4 and IL-12 in the development of lupus in NZB/W F1 mice." J.Immunol.158. 1466-1472 (1997)
[文献書誌] Seino,K.,et al.: "Antitumor effect of locally produced CD95 ligand." Nature Med.3. 165-170 (1997)
[文献書誌] Seino,K.,et al.: "Rejection of Fas Ligand-Expressing Grafts." Transplant.Proc.29. 1092-1093 (1997)
[文献書誌] Kayagaki,N.,et al.: "Polymorphism of murine Fas ligand that affects the biological activity." Proc.Natl.Acad.Sci.USA.94. 3914-3919 (1997)
[文献書誌] Yokoi,H.,et al.: "Prevention of experimental autoimmune uveoretinitis by monoclonal antibody to interleukin-12." Eur.J.Immunol.27. 641-646 (1997)
[文献書誌] Nakajima,A.,et al.: "Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells." Int.Immunol.9. 637-644 (1997)
[文献書誌] Hattori,K.,et al.: "A metalloproteinase inhibitor prevents lethal acute graft-versus-host disease in mice." Blood.90. 542-548 (1997)
[文献書誌] Maeda,K.,et al.: "Characterization of rat CD80 and CD86 by molecular cloning and mAb." Int.Immunol.9. 993-1000 (1997)
[文献書誌] Kawamura,T.,et al.: "Critical role of NK1^+ T cells in IL-12-induced immune resposes in vivo." The J.Immunol.160. 16-19 (1998)

1997 年度 実績報告書

リンパ球機能分子(LFA)を介したT細胞の分子誘導と活性化機序の解析

研究代表者

奥村 康 順天堂大学, 医学部, 教授 (50009700)

研究成果

[文献書誌] Noto,K.,et al.: "Identification and functional characterization of mouse CD29 with a mAb." Int.Immunol.7. 835-842 (1995)

[文献書誌] Lanier,L.L.,et al.: "CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation,cytokine production,and generation of CTL^1." J.Immunol.154. 97-105 (1995)

[文献書誌] Yasuda,M.,et al.: "Expression and function of fibronectin binding integrins on rat mast cells." Int.Immunol.7. 251-258 (1995)

[文献書誌] Azuma,A.,et al.: "Augmented lung adenocarcinoma cytotoxicity by the combination of a genetically modified anti-Lewis Y antibody and antibodies to complement regulatory proteins." Scand.J.Immunol.42. 202-208 (1995)

[文献書誌] Ushiyama,C.,et al.: "Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantaion." J.Immunol.154. 2687-2696 (1995)

[文献書誌] Yagita,H.,et al.: "Fas-mediated cytotoxicity-a new immunoregulatory and pathogenic function of Thl CD4 T cells." Immunological Reviews. 146. 223-239 (1995)

[文献書誌] Seino,K.,et al.: "CD86 (B70/B7-2) on endothelial cells co-stimulates allogeneic CD4^+ T cells." Int Immunol.7. 1331-1337 (1995)

[文献書誌] Tanaka,T.,et al.: "Involvement of α1 and α4 integrins in gut mucosal injury of graft-versus-host disease." Int Immunol.7. 1183-1189 (1995)

[文献書誌] Kayagaki,N.et al.: "Metalloproteinase-mediated release of human Fas ligand." J.Exp.Med.182. 1777-1783 (1995)

[文献書誌] Nakajima,A.,et al.: "Preferential dependence of autoantibody production in murine lupus on CD86 co-stimulatory molecule." Eur.J.Immunol.25. 3060-3069 (1995)

[文献書誌] Bashuda,H.,et al.: "Induction of persistent allograft tolerance in the rat by combined treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies,donor specific transfusion,and FK506." Transplantation. 6. 117-122 (1996)

[文献書誌] Yonezawa,I.,et al.: "VLA-5 mediated interaction with fibronectin induces cytokine production by human chondrocytes." Biochem.Biophys.Res.Commur.219. 261-264 (1996)

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

[文献書誌] Kato,K.,et al.: "Local production of IL-12 p40 suppresses Th1-mediated immune responses and prevents allogeneic myoblast rejection." Proc.Natl.Acad.Sci.USA.93. 9085-9089 (1996)

[文献書誌] Bashuda,H.,et al.: "Specific acceptance of cardiac allografts after treatment with antibodies to CD80 and CD86 in mice." Transplantaion.28. 1039-1041 (1996)

[文献書誌] Nuriya,S.,et al.: "The differential role of CD86 and CD80 costimulatory molecules in the induction and the effector phases of contact hypersensitivity." Int.Immunol.8. 917-926 (1996)

[文献書誌] Nakano,H.,et al.: "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] Hamamura,K.,et al.: "A critical role of VLA-4 in erythropoiesis in vivo." Blood. 6. 2513-2517 (1996)

[文献書誌] Seino,K.,et al.: "Contribution of Fas ligand to cardiac allograft rejection." Int.Immunol.8. 1347-1354 (1996)

[文献書誌] Takazawa,K.,et al.: "Synergistic effects of mycophenolate Mofetil (MMF,RS-61443) and anti-LFA-1/monoclonal antibodies on the prolongation of heart allograft survival in rats." Transplantation. 28. 1980-1981 (1996)

[文献書誌] Sekine,C.,et al.: "Fas-mediated stimulation induces IL-8 secretion by rheumatoid arthritis synoviocytes independently of CPP32-mediated apoptosis." Biochem.Biophys.Res.Commun.228. 14-20 (1996)

[文献書誌] Saito,K.,et al.: "Effect of CD80 and CD86 blockade and anti-interleukin-12 treatment on mouse acute graft-vesus-host disease." Eur.J.Immunol.26. 3098-3106 (1996)

[文献書誌] Kaneko,H.,et al.: "Preferential elimination of CD28^+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis." Clin.Exp.Immunol.106. 218-229 (1996)

[文献書誌] Kaneko,Y.,et al.: "CD40-mediated stimulation of B1 and B2 cells : Implication in autoantibody production in murine lupus." Eur.J.Immunol.26. 3061-3065 (1996)

[文献書誌] Bashuda,H.,et al.: "Lack of cognate help by CD4^+ T cells and anergy of CD8^+ T cells are the principal mechanisms for anti-leukocyte function-associated antigen-l/intercellular adhesion molecule-l-induced cardiac allograft tolerance." Transplantation. 63. 113-118 (1997)

[文献書誌] Nakajima,A.,et al.: "Roles of IL^^--4 and IL-12 in the development of lupus in NZB/W F1 mice." J.Immunol.158. 1466-1472 (1997)

[文献書誌] Seino,K.,et al.: "Antitumor effect of locally produced CD95 ligand." Nature Med.3. 165-170 (1997)

[文献書誌] Seino,K.,et al.: "Rejection of Fas Ligand-Expressing Grafts." Transplant.Proc.29. 1092-1093 (1997)

[文献書誌] Kayagaki,N.,et al.: "Polymorphism of murine Fas ligand that affects the biological activity." Proc.Natl.Acad.Sci.USA.94. 3914-3919 (1997)

[文献書誌] Yokoi,H.,et al.: "Prevention of experimental autoimmune uveoretinitis by monoclonal antibody to interleukin-12." Eur.J.Immunol.27. 641-646 (1997)

[文献書誌] Nakajima,A.,et al.: "Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells." Int.Immunol.9. 637-644 (1997)

[文献書誌] Hattori,K.,et al.: "A metalloproteinase inhibitor prevents lethal acute graft-versus-host disease in mice." Blood.90. 542-548 (1997)

[文献書誌] Maeda,K.,et al.: "Characterization of rat CD80 and CD86 by molecular cloning and mAb." Int.Immunol.9. 993-1000 (1997)

[文献書誌] Kawamura,T.,et al.: "Critical role of NK1^+ T cells in IL-12-induced immune resposes in vivo." The J.Immunol.160. 16-19 (1998)

1997 年度実績報告書

奥村康順天堂大学, 医学部, 教授 (50009700)