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2004 Fiscal Year Final Research Report Summary

Basic study of molecular target therapy for autoimmune diseases and immune deficiency diseases based on CD26

Research Project

Project/Area Number 15209033
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe University of Tokyo

Principal Investigator

MORIMOTO Chikao  The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (30119028)

Co-Investigator(Kenkyū-buntansha) HOSONO Osamu  The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (50190210)
KAWASAKI Hiroshi  The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (80280957)
Project Period (FY) 2003 – 2004
KeywordsCD26 / CD45RA / cord T cell / CD86 / interference RNA / Caveolin-1 / Tetanus Toxid / CD28
Research Abstract

CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. We investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells(CBTCs) and peripheral blood T cells(PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase(Lck), zeta-associated protein 70(ZAP-70), T-cell receptor zeta(TCRzeta), and linker for activator of T cells(LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible f … More or the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation.
We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid(TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201-211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-kappaB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation. Less

  • Research Products

    (11 results)

All 2005 2004 2003

All Journal Article (11 results)

  • [Journal Article] HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L).2005

    • Author(s)
      Iwata S, et al.
    • Journal Title

      Oncogene 24

      Pages: 1262-1271

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of p38 phosphorylation and topoisomerase IIalpha expression in the B-cell lymphoma line Jiyoye by CD26/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin.2005

    • Author(s)
      Yamochi T, et al.
    • Journal Title

      Cancer Res 65

      Pages: 1973-1983

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] HTLV-I Tax induces and associates with Crk-associated substrate lymphocyte type (Cas-L).2005

    • Author(s)
      Iwata S., et al.
    • Journal Title

      Oneogene 24

      Pages: 1262-1271

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of p38 phosphorylation and topoisomerase IIalpha expression in the B-cell lymphoma line Jiyoye by CD26/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin.2005

    • Author(s)
      Yamochi T., et al.
    • Journal Title

      Cancer Res. 65

      Pages: 1973-1983

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-12004

    • Author(s)
      Ohnuma K, et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 14186-14191

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation2004

    • Author(s)
      Kobayashi S, et al.
    • Journal Title

      Blood 103

      Pages: 1002-1010

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Preferential expression of CD9 on human CD4+CD45RA+ naive T cell population responsive to beta2-glycoprotein I.2004

    • Author(s)
      Kobayashi H, et al.
    • Journal Title

      Clin.Exp.Immunol 137

      Pages: 101-108

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1.2004

    • Author(s)
      Ohnuma K., et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 14186-14191

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of CD26 with CD45RA outside lipid rafts attenuates cord blood T-cell activation.2004

    • Author(s)
      Kobayashi S., et al.
    • Journal Title

      Blood 103

      Pages: 1002-1010

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G(2)/M arrest induced by topoisomerase II inhibitors.2003

    • Author(s)
      Aytac U., et al.
    • Journal Title

      Br J Cancer 88

      Pages: 455-462

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G(2)/M arrest induced by topoisomerase II inhibitors.2003

    • Author(s)
      Aytac U., et al.
    • Journal Title

      Br J Cancer. 88

      Pages: 455-462

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

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Published: 2006-07-11  

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