• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro

Research Project

Project/Area Number 15390132
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational Institute for Longevity Sciences (2005)
Tokyo Metropolitan Institute of Gerontology (2003-2004)

Principal Investigator

SHIMIZU Jun  National Institute for Longevity Sciences, Section of Immunology, Department of Mechanism of Aging, Section Chief, (研究所)・老化機構研究部免疫研究室, 室長 (60291134)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2005: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsAging / CD4 T cells / Immunoregulation
Research Abstract

CD4^+CD25^+ T cells have immunoregulatory and suppressive functions, and are responsible for suppressing self-reactive cells and maintaining self-tolerance. In addition to CD4^+CD25^+ T cells, there is also some evidence that a fraction of CD4^+CD25^- T cells exhibit suppressive activity in vitro or in vivo. We have shown using aged mice that aging not only leads to a decline in the ability to mount CD4^+CD25^- T cell responses, but at the same time, renders aged CD4^+CD25^- T cells suppressive. Here we report two newly established mAbs, which could abrogate the suppressive function of aged CD4^+CD25^- T cells. These mAbs recognized the same protein, the transmembrane phosphatase CD45. Cross-linking of CD45 on aged CD4^+CD25^- T cells was required for the disruption of their suppressive activity. Surprisingly, these mAbs also abrogated the suppressive action of CD4^+CD25^+ T cells in vitro. Our results demonstrate an unexpected function of CD45 as a negative regulator neutralizing the suppressive activity of aged CD4^+CD25^- and young CD4^+CD25^+ T cells.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004 2003 Other

All Journal Article (24 results) Publications (3 results)

  • [Journal Article] CD4+CD25+Foxp3+T cells and CD4+CD25-Foxp3+ T cells in aged mice2006

    • Author(s)
      Nishioka, T
    • Journal Title

      J.Immunol. 176

      Pages: 6586-6593

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of atuoimmune myocarditis and multi-organ inflammation by GITR^high,Foxp-expressing CD25^+ regulatory T cells2006

    • Author(s)
      Ono, M.
    • Journal Title

      J.Immunol. 176

      Pages: 4748-4756

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Proteinhigh, Foxp3-Expressing CD25+ and CD25- Regulatory T Cells.2006

    • Author(s)
      Ono M, Shimizu J, Miyachi Y, Sakaguchi S.
    • Journal Title

      J Immunol 176

      Pages: 4748-4756

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CD4+CD25+Foxp3+ T Cells and CD4+CD25-Foxp3+ T Cells in Aged Mice.2006

    • Author(s)
      Nishioka T, Shimizu J, Iida R, Yamazaki S, Sakaguchi S.
    • Journal Title

      J Immunol 176

      Pages: 6586-6593

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Control of autoimmune myocarditis and multi-organ inflammation by GITR^<high>, Foxp3-expressing CD25^+ and CD25^- regulatory T cells2006

    • Author(s)
      Ono, M.
    • Journal Title

      J.Immunol. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CD4^+CD25^+Foxp3^+ T cells and CD4^+CD25^-Foxp3^+ T cells in aged mice2006

    • Author(s)
      Nishioka, T.
    • Journal Title

      J.Immunol. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.2005

    • Author(s)
      Shimizu, J
    • Journal Title

      J.Immunol. 174

      Pages: 4090-4097

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] treatment of advanced tumors with agonistic anti-GITR m Ab and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells.2005

    • Author(s)
      Ko, K.
    • Journal Title

      J.Exp.Med. 202

      Pages: 885-891

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 加齢と免疫「わかりやすい免疫疾患」生涯教育シリーズ672005

    • Author(s)
      清水淳
    • Journal Title

      日本医師会雑誌特別号

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells.2005

    • Author(s)
      Ko K, Yamazaki S, Nakamura K, Nishioka T, Hirota K, Yamaguchi T, Shimizu J, Nomura T, Chiba T, Sakaguchi S.
    • Journal Title

      J Exp Med 202

      Pages: 885-891

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4+ and CD8+ T cells.2005

    • Author(s)
      Bian Y, Hiraoka S, Tomura M, Zhou XY, Yashiro-Ohtani Y, Mori Y, Shimizu J, Ono S, Dunussi-Joannopoulos K, Wolf S, Fujiwara H.
    • Journal Title

      Int Immunol 17

      Pages: 73-83

    • NAID

      10014258604

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.2005

    • Author(s)
      Shimizu J, Iida R, Sato Y, Moriizumi E, Nishikawa A, Ishida Y.
    • Journal Title

      J Immunol 174

      Pages: 4090-4097

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.2005

    • Author(s)
      Shimizu, J.
    • Journal Title

      J.Immunol. 174

      Pages: 4090-4097

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3^+CD25^+CD4^+ regulatory T cells.2005

    • Author(s)
      Ko, K.
    • Journal Title

      J.Exp.Med. 202

      Pages: 885-891

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 加齢と免疫.「わかりやすい免疫疾患」生涯教育シリーズ672005

    • Author(s)
      清水 淳
    • Journal Title

      日本医師会雑誌特別号

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4+ and CD8+ T cells.2005

    • Author(s)
      Bian, Y.
    • Journal Title

      Int.Immunol. 17

      Pages: 73-83

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4^+ and CD8^+ T cells.2005

    • Author(s)
      Bian Y
    • Journal Title

      Int.Immunol. 17

      Pages: 73-83

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cross-linking of CD45 on suppressive/regulatory T cells leads to the abrogation of their suppressive activity in vitro.2005

    • Author(s)
      Shimizu J
    • Journal Title

      J.Immunol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 加齢と免疫2005

    • Author(s)
      清水 淳
    • Journal Title

      生涯教育シリーズ67 日本医師会雑誌特別号 「わかりやすい免疫疾患」 (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 老化に伴う免疫抑制性CD4T細胞の出現2004

    • Author(s)
      清水淳
    • Journal Title

      基礎老化研究 28

      Pages: 15-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of autoimmune diabetes by non-islet-specific T cells - a role for the glucocorticoid-induced TNF receptor.2004

    • Author(s)
      Suri A, Shimizu J, Katz JD, Sakaguchi S, Unanue ER, Kanagawa O.
    • Journal Title

      Eur J Immunol 34

      Pages: 447-454

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 老化に伴う免疫抑制性CD4T細胞の出現2004

    • Author(s)
      清水 淳
    • Journal Title

      基礎老化研究 28

      Pages: 15-19

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Aging-dependent generation of suppressive CD4+CD25-R1231oCD103+ T cells in mice.2003

    • Author(s)
      Shimizu J, Moriizumi E.
    • Journal Title

      Eur J Immunol 33

      Pages: 2449-2458

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CD4+CD25- T cells in aged mice are hyporesponsive and exhibit suppressive activity.2003

    • Author(s)
      Shimizu J, Moriizumi E.
    • Journal Title

      J Immunol 170

      Pages: 1675-1682

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Suri A, Shimizu J, 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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu J, Morizumi E.: "Aging-dependent generation of suppressive CD4 CD25^-R123^<10>CD103^+T cells in mice."Eur.J.Immunol.. 33. 2449-2458 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu J, Moriizumi E.: "CD4^+CD25^-T cells in aged mice are hyporesponsive and exhibit suppressive activity."J.Immunol.. 170. 1675-1682 (2003)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi