2000 Fiscal Year Annual Research Report

自己免疫疾患を制御するNK-T細胞の分化と機能

Research Project

Project/Area Number	12470050
Research Institution	Hokkaido University
Principal Investigator	小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)
Co-Investigator(Kenkyū-buntansha)	柳川芳毅北海道大学, 遺伝子病制御研究所, 助手 (20322852) 岩渕和也北海道大学, 遺伝子病制御研究所, 助教授 (20184898)
Keywords	NK-T細胞 / 前駆細胞 / ZAP-70 / 胸腺器官培養 / 2Cトランスジェニックマウス
Research Abstract	T 細胞の分化・機能に必須のシグナル伝達分子、ZAP-70欠損マウスではNK-T細胞が産生されないことを明らかにした。このマウスの胸腺、脾臓では、その代わり正常マウスでは認められないNK1.1^+TCRαβ^-細胞が増加していた。このポピュレーションは通常のNK細胞、NK-T細胞とは異なるフェノタイプを示し、細胞傷害活性、INF-γ産生などのNK機能を持っていた。さらに、NK1.1^+TCRαβ^-細胞を新生児胸腺器官培養の系において、PMAとイオノマイシンで刺激すると、RAG mRNAの発現が認められ、TCR遺伝子の再配列が誘導され、NK-T細胞へと分化した。従って、これらNK1.1^+TCRαβ^-細胞は、NK-Tの前駆細胞であることが、判明した。次に2C TCRトランスジェニックマウスにおける、NK-T細胞の分化を解析し、これらのマウスでは、クロノタイプ陽性のCD8^+NK-T細胞が産生されることを発見した。これらCD8^+NK-T細胞は、MHCクラスI分子によって、正の選択を受けること、刺激によってINF-γは産生するが、IL-4は産生しないことが判明した。最後に、NK-T細胞がin vitroの補体処理によって、特異的に障害されることが判明した。この現象は、一部のSLEモデルマウスでも認められたが、B細胞、抗体の存在しないDO10/D2/RAG-/-マウスでは認められないことから、NK-T細胞には生体内で、自己抗体が結合していることが示唆された。

Research Products
(28 results)

All Other

All Publications (28 results)

[Publications] Kitaichi, N., Onoe, K.et al.: "Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies."Curr.Eye Res.. 20. 109-114 (2000)
[Publications] Ito.D., Onoe, K.et al.: "Induction of CTL responses by simultaneous administration of liposomal peptide vaccine with anti-CD40 and anti-CTLA-4 mAb."J.Immunol.. 164. 1230-1235 (2000)
[Publications] Ito.D., Onoe, K.et al.: "Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied with anti-CD40 and anti-CTLA-4 antibodies."Immunobiology.. 201. 527-540 (2000)
[Publications] Kizaki, T., Onoe, K.et al.: "Age-associated increase of basal corticoid levels decreases ED2^<high>,NF-κB^<high> activated macrophages."J.Leukocyte Biol.. 68. 21-30 (2000)
[Publications] Izutsu, Y., Onoe, K.et al.: "Loss of reactivity to pan-cadherin antibody in epidermal cells as a marker for metamorphic alteration of Xenopus skin."Dev.Growth.Diff.. 42(4). 377-383 (2000)
[Publications] Izutsu, Y., Onoe, K.et al.: "Larval antigen moleucles recognized by adult immune cells of inbred Xenopus laevis : Two pathways for recognition by adult splenic T cells."Dev.Biol.. 221. 365-374 (2000)
[Publications] Tone.S., Onoe, K.et al.: "Induction of NK1.1^+αβTCR^+ T cells by bypassing TCR signals in ZAP-70 deficient mice."Immunology Letters. 73. 65-69 (2000)
[Publications] Morohashi, T., Onoe, K.et al.: "Abrogation of negative selection by GVHR induced by minor histocompatibility antigens or H-2D antigen alone."Immunobiology. 202. 268-279 (2000)
[Publications] Kitaichi, N., Onoe, K.et al.: "Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis."Br.J.Ophtalmol.. 84. 1423-1425 (2000)
[Publications] Namba, K., Onoe, K.et al.: "Amelioration of experimental autoimmune uveoretinitis (EAU) by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand mAb."J.Immunol.. 165. 2962-2969 (2000)
[Publications] Morohashi, T., Onoe, K.et al.: "Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from GVHD."Bone Marrow Transplant.. 26. 1069-1076 (2000)
[Publications] Kitaichi, N., Onoe, K.et al.: "Systemic high-dose corticosteroid administration induced high levels of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada's disease."Microbiol.Immunol.. 44. 1075-1077 (2000)
[Publications] Konishi, J., Onoe, k.et al.: "Thymic epithelial cells responsible for impaired generation of NK-T thymocytes in alymphoplasia mutant mice."Cell.Immunol.. 206. 26-35 (2000)
[Publications] 小野江和則: "(解説)キラーT細胞活性化における骨髄由来抗原提示細胞の役割(Cross-presentation)."臨床免疫.. 33. 384-388 (2000)
[Publications] 伊藤大祐: "抗CD40及び抗CTLA-4モノクロナール抗体と抗腫瘍ペプチドワクチン同時投与による細胞傷害性T細胞誘導."臨床免疫. 33. 566-572 (2000)
[Publications] 岩渕和也: "CD161 (NKR-P1A)."臨床免疫.. 34(別冊19). 249-254 (2000)
[Publications] Iwabuchi, K., Onoe, K.et al.: "Defective development of NK1.1^+ T cell antigen receptor (TCR) αβ^+ cells in zeta-associated protein (ZAP) null mice with an accumulation of NK1.1^+CD3^-NK-like cells in the thymus."Blood. (in press).
[Publications] Ohwatari, R., Onoe, K.et al.: "Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener's granulomatosis and relapsing polychondritis."Annals of Otology, Rhinology & Larygology.. (in press).
[Publications] Ishimori, N., Onoe, K.et al.: "Mixed allogeneic chimerism with wild-type strains ameliorated atherosclerosis in apolipoprotein E-deficient mice."J.Leukocyte Biol.. (in press).
[Publications] Mishima, M., Onoe, K.et al.: "Tolerogen-producing cells in allogeneic bone marrow chimeras established with spontaneously leukemia-prone mice."J.Clin.Exp.Hemathopathol.. (in press).
[Publications] Niino, M., Onoe, K.et al.: "Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-γ."J.Neuroimmunol.. (in press).
[Publications] 小野江和則: "「移植医療」"北海道医師会. 5 (2000)
[Publications] 小野江和則: "「運動生理・生化学辞典」"大修館書店(印刷中).
[Publications] 岩渕和也: "「運動生理・生化学辞典」"大修館書店(印刷中).
[Publications] 小野江和則: "免疫寛容"日本医学館(印刷中).
[Publications] 小野江和則: "「免疫学辞典」"東京化学同人(印刷中).
[Publications] 小野江和則: "「医学大辞典」"医学書院(印刷中).
[Publications] Onoe, K.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse, The Netherlands (in press).

2000 Fiscal Year Annual Research Report

自己免疫疾患を制御するNK-T細胞の分化と機能

Principal Investigator

小野江 和則 北海道大学, 遺伝子病制御研究所, 教授 (40002117)

Research Products

[Publications] Kitaichi, N., Onoe, K.et al.: "Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies."Curr.Eye Res.. 20. 109-114 (2000)

[Publications] Ito.D., Onoe, K.et al.: "Induction of CTL responses by simultaneous administration of liposomal peptide vaccine with anti-CD40 and anti-CTLA-4 mAb."J.Immunol.. 164. 1230-1235 (2000)

[Publications] Ito.D., Onoe, K.et al.: "Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied with anti-CD40 and anti-CTLA-4 antibodies."Immunobiology.. 201. 527-540 (2000)

[Publications] Kizaki, T., Onoe, K.et al.: "Age-associated increase of basal corticoid levels decreases ED2^<high>,NF-κB^<high> activated macrophages."J.Leukocyte Biol.. 68. 21-30 (2000)

[Publications] Izutsu, Y., Onoe, K.et al.: "Loss of reactivity to pan-cadherin antibody in epidermal cells as a marker for metamorphic alteration of Xenopus skin."Dev.Growth.Diff.. 42(4). 377-383 (2000)

[Publications] Izutsu, Y., Onoe, K.et al.: "Larval antigen moleucles recognized by adult immune cells of inbred Xenopus laevis : Two pathways for recognition by adult splenic T cells."Dev.Biol.. 221. 365-374 (2000)

[Publications] Tone.S., Onoe, K.et al.: "Induction of NK1.1^+αβTCR^+ T cells by bypassing TCR signals in ZAP-70 deficient mice."Immunology Letters. 73. 65-69 (2000)

[Publications] Morohashi, T., Onoe, K.et al.: "Abrogation of negative selection by GVHR induced by minor histocompatibility antigens or H-2D antigen alone."Immunobiology. 202. 268-279 (2000)

[Publications] Kitaichi, N., Onoe, K.et al.: "Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis."Br.J.Ophtalmol.. 84. 1423-1425 (2000)

[Publications] Namba, K., Onoe, K.et al.: "Amelioration of experimental autoimmune uveoretinitis (EAU) by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand mAb."J.Immunol.. 165. 2962-2969 (2000)

[Publications] Morohashi, T., Onoe, K.et al.: "Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from GVHD."Bone Marrow Transplant.. 26. 1069-1076 (2000)

[Publications] Kitaichi, N., Onoe, K.et al.: "Systemic high-dose corticosteroid administration induced high levels of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada's disease."Microbiol.Immunol.. 44. 1075-1077 (2000)

[Publications] Konishi, J., Onoe, k.et al.: "Thymic epithelial cells responsible for impaired generation of NK-T thymocytes in alymphoplasia mutant mice."Cell.Immunol.. 206. 26-35 (2000)

[Publications] 小野江和則: "(解説)キラーT細胞活性化における骨髄由来抗原提示細胞の役割(Cross-presentation)."臨床免疫.. 33. 384-388 (2000)

[Publications] 伊藤大祐: "抗CD40及び抗CTLA-4モノクロナール抗体と抗腫瘍ペプチドワクチン同時投与による細胞傷害性T細胞誘導."臨床免疫. 33. 566-572 (2000)

[Publications] 岩渕和也: "CD161 (NKR-P1A)."臨床免疫.. 34(別冊19). 249-254 (2000)

[Publications] Iwabuchi, K., Onoe, K.et al.: "Defective development of NK1.1^+ T cell antigen receptor (TCR) αβ^+ cells in zeta-associated protein (ZAP) null mice with an accumulation of NK1.1^+CD3^-NK-like cells in the thymus."Blood. (in press).

[Publications] Ohwatari, R., Onoe, K.et al.: "Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener's granulomatosis and relapsing polychondritis."Annals of Otology, Rhinology & Larygology.. (in press).

[Publications] Ishimori, N., Onoe, K.et al.: "Mixed allogeneic chimerism with wild-type strains ameliorated atherosclerosis in apolipoprotein E-deficient mice."J.Leukocyte Biol.. (in press).

[Publications] Mishima, M., Onoe, K.et al.: "Tolerogen-producing cells in allogeneic bone marrow chimeras established with spontaneously leukemia-prone mice."J.Clin.Exp.Hemathopathol.. (in press).

[Publications] Niino, M., Onoe, K.et al.: "Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-γ."J.Neuroimmunol.. (in press).

[Publications] 小野江和則: "「移植医療」"北海道医師会. 5 (2000)

[Publications] 小野江和則: "「運動生理・生化学辞典」"大修館書店(印刷中).

[Publications] 岩渕和也: "「運動生理・生化学辞典」"大修館書店(印刷中).

[Publications] 小野江和則: "免疫寛容"日本医学館(印刷中).

[Publications] 小野江和則: "「免疫学辞典」"東京化学同人(印刷中).

[Publications] 小野江和則: "「医学大辞典」"医学書院(印刷中).

[Publications] Onoe, K.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse, The Netherlands (in press).

小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)