2003 Fiscal Year Annual Research Report

NK-T細胞の分化と免疫系制御で働く分子の同定

Research Project

Project/Area Number	14104010
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 / 樹状細胞 / SMLR / 自己抗体 / 補体感受性 / ケモカイン / 動脈硬化症 / CD1d
Research Abstract	前年度、生体内でNK-T細胞に特異的自己抗体が結合することを発見し、このような自己抗体産生は、NK-T細胞の自己反応性に起因することを提唱した。しかし、同様の現象が、OVA特異的、I-A^d拘束性T細胞レセプター(TCR)トランスジェニックマウス(DO10)でも認められ、B細胞、抗体の存在しないRAG-/-/DO10マウスでは認められないことが判明した。DO10は我々が報告した、NK-T細胞がMHCクラスII拘束性TCR(KJ1-26^+)を発現する世界で唯一のマウス系である。従って、KJ1-26^+NK-T特異的自己抗体産生を単純にNK-T細胞の自己反応性で説明できない。今年度はこの一見不思議な現象のメカニズムを解明するために、KJ1-26^+NK-T細胞と、KJ1-26^+メインストリームT細胞の反応性を比較・解析した。その結果、驚くべきことにKJ1-26^+NK-T細胞が、OVAと同時にCD1d分子にも反応性を示すことが判明した。またこれらの反応性をKJ1-26^+メインストリームT細胞のものと比べると、NK-T細胞はCD1dにはより強く、OVAとI-A^dには弱く反応した。これらの結果は、非多形性CD1dに対する自己反応性によって、NK-Tへ分化するか、メインストリームT細胞に分化するかが決定されることを示す。実際、種々のH-2、クラスI-/-、クラスII-/-マウスをドナー、またはホストにした骨髄キメラの解析から、KJ1-26^+NK-T細胞は造血細胞上のCD1d分子によって正の選択を受けることが判明した。KJ1-26^+NK-T細胞と、メインストリームT細胞の反応差を規定する分子の解明は、今後の重要課題である。次に、NK-T細胞が動脈硬化促進的に働くことを明らかにし、NK-T異常を示す新規マウスを発見した。また、前年に引き続き、NK-T細胞と樹状細胞の反応を解析するため、樹状細胞の機能を制御する戦略を開発した。

Research Products

(26 results)

All Other

All Publications (26 results)

[Publications] Zierhut, M.: "Human genome and diseases : Review "Immunology and functional genomics of Behcet's disease.""Cell.Mol.Life Sci.. 60. 1903-1922 (2003)
[Publications] Kikuchi, K.: "Tumour necrosis factor-α but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation."Immunology. 108. 42-49 (2003)
[Publications] Onoe, K.: "Positive and negative selection of T cell repertoires during differentiation in allogeneic bone marrow chimeras."Transplant Immunol.. 12. 79-83 (2003)
[Publications] Shimada, S.: "Expression of allograft inflammatory factor-1 in mouse uterus and poly (I : C)-induced fetal resorption."Am.J.Repro.Immunol.. 50. 104-112 (2003)
[Publications] Shimada, S.: "No difference in natural-killer-T cell population, but Th2/Tc2 predominance in peripheral blood of recurrent aborters."Am.J.Repro.Immunol.. 50. 334-339 (2003)
[Publications] Yanagawa, Y.: "CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities."Blood. 101. 4923-4929 (2003)
[Publications] Tosa, N.: "Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis."Int.Immunol.. 15. 741-749 (2003)
[Publications] Nakayama, K.: "Impaired degradation of IκB and β-catenin as a result of targeted disruption of the β TrCP1 gene."Proc.Nati.Acad.Sci.USA.. 100. 8752-8757 (2003)
[Publications] Kikuchi, K.: "Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells."Immunol.Lett.. 89. 149-154 (2003)
[Publications] Morohashi, T.: "Allograft inflammatory factor-1 (AIF-1) regulates trinitrobenzene sulfonic asid (TNBS) -induced colitis."Immunology. 110. 112-119 (2003)
[Publications] Pavlinkova, G.: "Effects of histamine on functional maturation of dendritic cells."Immunobiology. 207. 315-325 (2003)
[Publications] Iijima, N.: "Selective regulation of CD4O expression in murine dendritic cells by thiol antioxidants"Immunology. 110. 197-203 (2003)
[Publications] Iijima, N.: "Role of early and late phase activation of p38 MARK induced by TNF-α or 2,4-dinitrobenzene during maturation of dendritic cells."Immunology. 110. 322-328 (2003)
[Publications] Yamada, H.: "Decrease in a specific killer cell immunoglobulin-like receptor on peripheral natural killer cells in women with recurrent miscarriage of unexplained etiology."Am.J.Reprod.Immunol.. 50. 149-154 (2003)
[Publications] Nagafuku, M.: "Reduction of glycosphingolipid levels in lipid rafts affects the expression state and function of glycosylphosphatidylinositol-anchored proteins but does not impair signal transduction via the T cell receptor."J.Biol.Chem.. 278. 51920-51927 (2003)
[Publications] Nagashima, T.: "Analysis of T cell responses to a superantigen, staphylococcal enterotoxin B."J.Clin.Exp.Hematopathol.. (in press).
[Publications] Onoe, K.: "T cell differentiation in allogeneic bone marrow chimeras."Cancer Detection and Prevention. (in press).
[Publications] Takagi, D.: "Immuno-regulatory defects of Vα24^+Vβ11^+ NKT cells in development of Wegener's granulomotosis and relapsing polychondritis."Clin.Exp.Immunol.. (in press).
[Publications] 北市伸義: "NK細胞消去による実験的自己免疫性網膜ぶどう膜炎の軽症化"日本眼科学会雑誌. (印刷中).
[Publications] 菊地一博: "TNF-αによって修飾される樹状細胞の分化と機能"臨床免疫. 40. 126-132 (2003)
[Publications] 柳川芳毅: "樹状細胞機能に対するケモカインの効果"臨床免疫. 40. 415-419 (2003)
[Publications] 小野江和則: "医学大辞典"医学書院. 3062 (2003)
[Publications] Onoe, K.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse. 120 (2003)
[Publications] 小野江和則: "New Mook眼科,眼の自己免疫疾患"金原出版. 187 (2003)
[Publications] 小野江和則: "肝臓移植の実際"日本医京(印刷中).
[Publications] 岩渕和也: "モデル動物の作成と維持"エル・アイ・シー(印刷中).

2003 Fiscal Year Annual Research Report

NK-T細胞の分化と免疫系制御で働く分子の同定

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] Zierhut, M.: "Human genome and diseases : Review "Immunology and functional genomics of Behcet's disease.""Cell.Mol.Life Sci.. 60. 1903-1922 (2003)

[Publications] Kikuchi, K.: "Tumour necrosis factor-α but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation."Immunology. 108. 42-49 (2003)

[Publications] Onoe, K.: "Positive and negative selection of T cell repertoires during differentiation in allogeneic bone marrow chimeras."Transplant Immunol.. 12. 79-83 (2003)

[Publications] Shimada, S.: "Expression of allograft inflammatory factor-1 in mouse uterus and poly (I : C)-induced fetal resorption."Am.J.Repro.Immunol.. 50. 104-112 (2003)

[Publications] Shimada, S.: "No difference in natural-killer-T cell population, but Th2/Tc2 predominance in peripheral blood of recurrent aborters."Am.J.Repro.Immunol.. 50. 334-339 (2003)

[Publications] Yanagawa, Y.: "CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities."Blood. 101. 4923-4929 (2003)

[Publications] Tosa, N.: "Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis."Int.Immunol.. 15. 741-749 (2003)

[Publications] Nakayama, K.: "Impaired degradation of IκB and β-catenin as a result of targeted disruption of the β TrCP1 gene."Proc.Nati.Acad.Sci.USA.. 100. 8752-8757 (2003)

[Publications] Kikuchi, K.: "Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells."Immunol.Lett.. 89. 149-154 (2003)

[Publications] Morohashi, T.: "Allograft inflammatory factor-1 (AIF-1) regulates trinitrobenzene sulfonic asid (TNBS) -induced colitis."Immunology. 110. 112-119 (2003)

[Publications] Pavlinkova, G.: "Effects of histamine on functional maturation of dendritic cells."Immunobiology. 207. 315-325 (2003)

[Publications] Iijima, N.: "Selective regulation of CD4O expression in murine dendritic cells by thiol antioxidants"Immunology. 110. 197-203 (2003)

[Publications] Iijima, N.: "Role of early and late phase activation of p38 MARK induced by TNF-α or 2,4-dinitrobenzene during maturation of dendritic cells."Immunology. 110. 322-328 (2003)

[Publications] Yamada, H.: "Decrease in a specific killer cell immunoglobulin-like receptor on peripheral natural killer cells in women with recurrent miscarriage of unexplained etiology."Am.J.Reprod.Immunol.. 50. 149-154 (2003)

[Publications] Nagafuku, M.: "Reduction of glycosphingolipid levels in lipid rafts affects the expression state and function of glycosylphosphatidylinositol-anchored proteins but does not impair signal transduction via the T cell receptor."J.Biol.Chem.. 278. 51920-51927 (2003)

[Publications] Nagashima, T.: "Analysis of T cell responses to a superantigen, staphylococcal enterotoxin B."J.Clin.Exp.Hematopathol.. (in press).

[Publications] Onoe, K.: "T cell differentiation in allogeneic bone marrow chimeras."Cancer Detection and Prevention. (in press).

[Publications] Takagi, D.: "Immuno-regulatory defects of Vα24^+Vβ11^+ NKT cells in development of Wegener's granulomotosis and relapsing polychondritis."Clin.Exp.Immunol.. (in press).

[Publications] 北市伸義: "NK細胞消去による実験的自己免疫性網膜ぶどう膜炎の軽症化"日本眼科学会雑誌. (印刷中).

[Publications] 菊地一博: "TNF-αによって修飾される樹状細胞の分化と機能"臨床免疫. 40. 126-132 (2003)

[Publications] 柳川芳毅: "樹状細胞機能に対するケモカインの効果"臨床免疫. 40. 415-419 (2003)

[Publications] 小野江 和則: "医学大辞典"医学書院. 3062 (2003)

[Publications] Onoe, K.: "Immunology of Behcet's Disease"Swets & Zeitlinger, Lisse. 120 (2003)

[Publications] 小野江和則: "New Mook眼科,眼の自己免疫疾患"金原出版. 187 (2003)

[Publications] 小野江和則: "肝臓移植の実際"日本医京(印刷中).

[Publications] 岩渕和也: "モデル動物の作成と維持"エル・アイ・シー(印刷中).

小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)

[Publications] 小野江和則: "医学大辞典"医学書院. 3062 (2003)