2003 Fiscal Year Annual Research Report

制御性T細胞による免疫自己寛容維持機構の解析とその機能操作による自己免疫の修復

Research Project

Project/Area Number	13140203
Research Institution	Kyoto University
Principal Investigator	坂口志文京都大学, 再生医科学研究所, 教授 (30280770)
Co-Investigator(Kenkyū-buntansha)	中野直子東京理科大学, 生命科学研究所, 助教授 (90222166)
Keywords	制御性T細胞 / Foxp3
Research Abstract	制御性T細胞の発生・分化および機能の分子的基礎について、昨年度に引き続き研究を進め以下の研究結果を得た。 (1)昨年度、マウスFoxp3遺伝子が制御性T細胞のマスターコントロール遺伝子であることを報告した。本年度、ヒトFOXP3遺伝子がヒトCD25^+CD4^+制御性T細胞に選択的に発現しており、正常T細胞にレトロウイルスベクターでFOXP3遺伝子を導入すると、ヒトナイーブT細胞を表現型,機能がCD25^+CD4^+制御性T細胞と相同の細胞に転化できることを見出した。 (2)抗GITR抗体の抗腫瘍効果の解析を進めた。またGITRのリガンドであるGITR-Lについてその遺伝子を同定し、遺伝子欠損マウスを作製した。またGITR-Lに対する単クローン性抗体を作製した。これらを用いて、現在GITR-Lの機能を解析している。 (3)CD25^+CD4^+制御性T細胞活性化における樹状細胞の役割を解析した。成熟樹状細胞上で制御性T細胞が増殖でき、その際共刺激分子からの刺激が必要であることを見出した。現在、未熟樹状細胞上に発現するGITR-Lの役割を含め解析中である。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Suri A, Sakaguchi S, et al.: "Regulation of autoimmune diabetes by non-islet-specific T cells-a role for the glucocorticoid-induced TNF receptor."Eur.J.Immunol.. 34. 447-454 (2004)
[Publications] Kajiura F, Sakaguchi S, et al.: "NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner."J.Immunol.. 172. 2067-2075 (2004)
[Publications] Zhand X, Sakaguchi S. et al.: "IL-10is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+regulatory T cells."Int.Immunology. 16. 249-256 (2004)
[Publications] Fehervari Z, Sakaguchi S: "Development and function of CD25+CD4+regulatory T cells."Curr.Opinion in Immunol.. 16. 1-6 (2004)
[Publications] Fehervari Z, Sakaguchi S: "A paragon of selt-tolerance : Regulatory T cells and the control of immune responses."Arthritis.Res.Ther.. 6. 19-25 (2004)
[Publications] Sakaguchi S: "Naturally arising CD4+regulatory T cells for immunologic self-tolerance and negative control of immune responses."Ann.Rev.Immunol.. 22. 17.1-17.32 (2004)
[Publications] Sakaguchi N, Sakaguchi S, et al.: "Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice."Nature. 426. 454-460 (2003)
[Publications] Sakaguchi S: "The origin of FOXP3-expressing CD4+regulatory T cells : thymus or periphery."J.Clin.Invest.. 112. 1310-1312 (2003)
[Publications] Sakaguchi S: "Taming transplantation by regulartory T cells."Nature Medicine. 9. 1117-1118 (2003)
[Publications] Hori S, Sakaguchi S, et al.: "Control of autoimmunity by natural regulatory T cells."Adv.Immunol.. 81. 331-371 (2003)
[Publications] Takahashi T, Sakaguchi S: "Naturally arising CD25+CD4+regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease."Curr.Mol.Med.. 3. 693-706 (2003)
[Publications] Wood K, Sakaguchi S: "Regulatory T cells in transplantation."Nature Rev.Immunol.. 3. 199-210 (2003)
[Publications] Takahashi T, Sakaguchi S: "The role of regulatory T cells in controlling immunologic self-tolerance."Int.Rev.Cytol.. 225. 1-32 (2003)

2003 Fiscal Year Annual Research Report

制御性T細胞による免疫自己寛容維持機構の解析とその機能操作による自己免疫の修復

Principal Investigator

坂口 志文 京都大学, 再生医科学研究所, 教授 (30280770)

Research Products

[Publications] Suri A, Sakaguchi S, et al.: "Regulation of autoimmune diabetes by non-islet-specific T cells-a role for the glucocorticoid-induced TNF receptor."Eur.J.Immunol.. 34. 447-454 (2004)

[Publications] Kajiura F, Sakaguchi S, et al.: "NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner."J.Immunol.. 172. 2067-2075 (2004)

[Publications] Zhand X, Sakaguchi S. et al.: "IL-10is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+regulatory T cells."Int.Immunology. 16. 249-256 (2004)

[Publications] Fehervari Z, Sakaguchi S: "Development and function of CD25+CD4+regulatory T cells."Curr.Opinion in Immunol.. 16. 1-6 (2004)

[Publications] Fehervari Z, Sakaguchi S: "A paragon of selt-tolerance : Regulatory T cells and the control of immune responses."Arthritis.Res.Ther.. 6. 19-25 (2004)

[Publications] Sakaguchi S: "Naturally arising CD4+regulatory T cells for immunologic self-tolerance and negative control of immune responses."Ann.Rev.Immunol.. 22. 17.1-17.32 (2004)

[Publications] Sakaguchi N, Sakaguchi S, et al.: "Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice."Nature. 426. 454-460 (2003)

[Publications] Sakaguchi S: "The origin of FOXP3-expressing CD4+regulatory T cells : thymus or periphery."J.Clin.Invest.. 112. 1310-1312 (2003)

[Publications] Sakaguchi S: "Taming transplantation by regulartory T cells."Nature Medicine. 9. 1117-1118 (2003)

[Publications] Hori S, Sakaguchi S, et al.: "Control of autoimmunity by natural regulatory T cells."Adv.Immunol.. 81. 331-371 (2003)

[Publications] Takahashi T, Sakaguchi S: "Naturally arising CD25+CD4+regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease."Curr.Mol.Med.. 3. 693-706 (2003)

[Publications] Wood K, Sakaguchi S: "Regulatory T cells in transplantation."Nature Rev.Immunol.. 3. 199-210 (2003)

[Publications] Takahashi T, Sakaguchi S: "The role of regulatory T cells in controlling immunologic self-tolerance."Int.Rev.Cytol.. 225. 1-32 (2003)

坂口志文京都大学, 再生医科学研究所, 教授 (30280770)