Functional analysis of CD4 T cell-subpopulation exhibiting low responsiveness in aged hosts

• Project/Area Number: 18390127
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto University (2008); National Institute for Longevity Sciences,NCGG (2006-2007)
• Principal Investigator: SHIMIZU Jun Kyoto University, 医学研究科, 准教授 (60291134)
• Co-Investigator(Kenkyū-buntansha): NISHIOKA Tomohisa 国立長寿医療センター(研究所), 老化機構研究部, 流動研究員 (50419149)
• Research Collaborator: YAMAZAKI Sayuri アメリカ, ロックフェラー大学, 博士研究員
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,260,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥2,760,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
• Keywords: 細胞 / 老化 / 免疫 / T細胞

Research Abstract

老齢B6 マウス(6ヶ月、12ヶ月、24ヶ月齢)をモデルとして用いた解析から、老化に伴いある特定のCD4T細胞亜集団の割合が増加し、しかもこの亜集団はT 細胞活性化誘導に対し著しい低応答性を呈すことを示してきた。今回この亜集団の低応答性を正常な高応答性へと回復させ得る培養条件を検討したが、本亜集団の活性化には持続的活性化刺激が必要であること、また本亜集団の出現にはT 細胞が抗原に暴露される必要性はなく、また酸化ストレスの持続的存在も関与していないことを示唆する結果が得られた。

Research Products

• [Journal Article] Antigen-independent generation of a unique CD4 T cell-subset with aging and its persistent unresponsiveness (2008)
  • Author(s): Nishida E, Nishioka T, Iida R, Yagita H, Morita A, Shimizu J
  • Journal Title: Immunol Lett 121 Pages: 27-32
  • Peer Reviewed
• [Journal Article] In vivo expansion of CD4^+Foxp3^+ regulatory T cells mediated by GITR molecules. (2008)
  • Author(s): Nishioka T, Nishida E, Iida R, Morita A, Shimizu J
  • Journal Title: Immunol Lett 121 Pages: 97-104
  • Peer Reviewed
• [Journal Article] Antigen-independent generation of a unique CD4 T cells subset with aging and its persistent unresponsiveness. (2008)
  • Author(s): Nishida E
  • Journal Title: Immunol Lett. 121 Pages: 27-32
  • Peer Reviewed
• [Journal Article] In vivo expansion of CD4+FoxP3+ regulatory T cells mediated by GITR molecules. (2008)
  • Author(s): Nishioka T
  • Journal Title: Immunol Lett. 121 Pages: 97-104
  • Peer Reviewed
• [Journal Article] Ohno-Iwashita Y. Impairment in a negative regulatory system for TCR signaling in CD4^+ T cells from old mice (2007)
  • Author(s): Inomata M, Shimada Y, Hayashi M, Shimizu J
  • Journal Title: FEBS Lett 581 Pages: 3039-3043
  • Peer Reviewed
• [Journal Article] Impairment in a negative regulatory system for TCR signaling in CD4^+ T cells from old mice. (2007)
  • Author(s): Inomata M,
  • Journal Title: FEBS Lett 581 Pages: 3039-3043
  • Peer Reviewed
• [Journal Article] TNFファミリー分子の分子リウマチ学:GITRL / GITR. (2007)
  • Author(s): 清水 淳、
  • Journal Title: 分子リウマチ(先端医学社) 4 Pages: 324-329
• [Journal Article] 高齢個体の免疫. (2007)
  • Author(s): 西岡朋尚、
  • Journal Title: 臨床免疫・アレルギー科(科学評論社) 47 Pages: 585-591
  • NAID: 130006949157
• [Journal Article] CD4T細胞の加齢変化. (2007)
  • Author(s): 西岡朋尚、
  • Journal Title: 臨床免疫・アレルギー科(科学評論社) 47 Pages: 477-483
  • NAID: 40015482719
• [Journal Article] Foxp3^+CD25^+CD4^+ natural regulatory T cells in dominant self-tolerance and autoimmune disease (2006)
  • Author(s): Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T
  • Journal Title: Immunol Rev 212 Pages: 8-27
  • Peer Reviewed
• [Journal Article] Control of autoimmune myocarditis and multi-organ inflammation by GITRhigh Foxp3-expressing CD25+ and CD25- regulatory T cells (2006)
  • Author(s): Ono M, Shimizu J, Miyachi Y, and Sakaguchi S
  • Journal Title: J. Immunol 176 Pages: 4748-4756
  • Peer Reviewed
• [Journal Article] Iida R, Yamazaki S, and Sakaguchi S. CD4^+CD25^+Foxp3^+ T cells and CD4^+CD^25-Foxp3^+ T cells in aged mice (2006)
  • Author(s): Nishioka T, Shimizu J
  • Journal Title: J. Immunol 176 Pages: 6586-6593
  • Peer Reviewed
• [Journal Article] COntrol of autoimmune myocarditis and multiorgan inflammation by gluvovorticoid-induced TNF receptor family-related protein^<high>, Foxp3-expressing CD25^+ and CD25^- regulatory T cells. (2006)
  • Author(s): Ono, M.
  • Journal Title: J Immunol 176 Pages: 4748-4756
• [Journal Article] CD4^+CD25^+Foxp3^+ T cells and CD4^+CD25^-Foxp3^+ T cells in aged mice. (2006)
  • Author(s): Nishidoka, T.
  • Journal Title: J Immunol 176 Pages: 6586-6593
• [Journal Article] Foxp3^+CD25^+CD4^+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. (2006)
  • Author(s): Sakaguchi, S.
  • Journal Title: Immunol Rev 212 Pages: 8-27
• [Presentation] Conversion of CD4^+Foxp3^-T cells into CD^4+Foxp^3+ T cells is inhibited by agonistic anti-GITR antibody (2008)
  • Author(s): Nishida E, Nishioka T, Iida R, Morita A, Shimizu J
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Conversion of CD4+Foxp3- T cells into CD4+Foxp3+T cells is inhibited by agonistic anti-GITR antibody. (2008)
  • Author(s): 西田絵美
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] 制御性CD4T細胞と同様の免疫抑制作用を呈す新規モノクローナル抗体の樹立 (2007)
  • Author(s): 西岡朋尚, 西田絵美, 清水淳
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] 新規抗GITR抗体による制御性CD4T細胞の増殖誘導 (2007)
  • Author(s): 西田絵美, 西岡朋尚, 森田明理, 清水淳
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] 制御性CD4T細胞と同様の免疫抑制作用を呈す新規モノクローナル抗体の樹立 (2007)
  • Author(s): 西岡朋尚,
  • Organizer: 日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] 新規抗GITR抗体による制御性CD4T細胞の増殖誘導 (2007)
  • Author(s): 西田絵美,
  • Organizer: 日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] (2007)
  • Author(s): 西岡朋尚、西田絵美、清水淳
  • Organizer: 第5回21世紀COE 若手研究フォーラムGITR を介する刺激で制御性T 細胞は増殖する
  • Place of Presentation: 名古屋大学医学部
  • Year and Date: 2007-06-07
• [Presentation] In vivo expansion of CD4^+Foxp3^+ regulatory T cells mediated by GITR molecules (2007)
  • Author(s): Shimizu J, Nishioka T, and Iida R
  • Organizer: Gordon Research Conferences
  • Place of Presentation: Los Angels
  • Year and Date: 2007-03-25
• [Presentation] In vivo expansion of CD4+Foxp3+ regulatory T cells mediated by GITR molecules (2007)
  • Author(s): 清水淳
  • Organizer: 京都大学再生医科学研究所 セミナー
  • Place of Presentation: 京都
  • Year and Date: 2007-02-23
• [Presentation] 老化と免疫抑制性T細胞 (2007)
  • Author(s): 清水淳
  • Organizer: 協和発酵(株)バイオフロンティア研究所セミナー
  • Place of Presentation: 東京
  • Year and Date: 2007-01-18
• [Presentation] CD4^+CD25^+Foxp3^+ T cells and CD4^+CD25^-Foxp3^+ T cells in aged mice (2006)
  • Author(s): Nishioka T, Iida R, and Shimizu J
  • Organizer: The 8^<th> International Congress of Neuroimmunology
  • Place of Presentation: Nagoya
  • Year and Date: 2006-10-15
• [Presentation] 高齢個体の免疫 (2006)
  • Author(s): 清水淳
  • Organizer: 第34回日本臨床免疫学会学術集会 シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2006-10-02
• [Presentation] 老化と免疫抑制性CD4T細胞 (2006)
  • Author(s): 清水淳
  • Organizer: 名古屋市立大学医学部皮膚科セミナー
  • Place of Presentation: 名古屋.
  • Year and Date: 2006-09-22
• [Presentation] Age-dependent reduction of PAG, a lipid raft-associated transmembrane adaptor protein, in mouse CD4 T cells (2006)
  • Author(s): Shimada Y, Inomata M, Hayashi M, Shimizu J, Ohno-Iwashita Y
  • Organizer: 20^<th> IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto
  • Year and Date: 2006-06-18
• [Presentation] 老化したCD4T 細胞では脂質ラフトを介した「負」のシグナル制御系に異常がある (2006)
  • Author(s): 猪股光司、嶋田有紀子、林昌美、清水淳、岩下淑子
  • Organizer: 第29回日本基礎老化学会
  • Place of Presentation: 長崎
  • Year and Date: 2006-06-16
• [Presentation] CD45 molecules as a functional modulator of regulatory CD4 T cells (2006)
  • Author(s): Shimizu J, Iida R, Nishioka T
  • Organizer: Immunology 2006
  • Place of Presentation: Boston
  • Year and Date: 2006-05-15
• [Book] 高齢個体の免疫 (2007)
  • Author(s): 西岡朋尚、清水淳
  • Publisher: 臨床免疫・アレルギー科
• [Book] CD4T細胞の加齢変化 (2007)
  • Author(s): 西岡朋尚、清水淳
  • Publisher: 臨床免疫・アレルギー科
• [Book] 坂口志文 分子リウマチ (2007)
  • Author(s): 清水淳
  • Publisher: GITRL / GITR のCD4T細胞機能への作用