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2005 Fiscal Year Final Research Report Summary

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
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.

  • Research Products

    (14 results)

All 2006 2005 2004 2003

All Journal Article (14 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

      Pages: S106-110

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2008-05-27  

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