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Regulatory mechanism of T cell development by pre-T cell specific transcription factors

Research Project

Project/Area Number 13470068
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

SAITO Takashi  Chiba University, Graduate School Of Medicine, Professor, 大学院・医学研究院, 教授 (50205655)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Sho  Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (40312946)
高瀬 完  千葉大学, 大学院・医学研究院, 助手 (40333489)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywordsthymic differentiation / pre T cell receptor / pTα chain / knockout mouse / lipid raft / transgenic mouse / Th1 / Th2 / Th2 / Ebox / E2A / HEB / プロモーター / 転写制御
Research Abstract

Signal regulation through the pre-TCR complex was analyzed n approaches ; one is to analyze a new molecule RIT which was cloned last year, two and the other is the analysis of pre-TCR signaling through lipid raft by preparing raft-residential chimeric molecule.
(1) RIT was cloned by DNA subtraction from pTα-expressing cells and is expressed only on CD25^+ immature thymocytes. RIT-KO mice were generated. By crossing with HY-specific TCR-Tg mice, RIT was found to modulate thymic selection.
(2) To prepare raft-residential protein, we made LAT-CD3εchimeric molecule. This molecule is indeed localized exclusively in lipid raft. By crossing with Rag-KO mice, the expression of LAT-CD3εaugumented development of DP thymocytes.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] Arase, H.: "Negative regulation of expression and function of FcγRIII by CD3ζ in murine NK cells."J.Immunol.. 166・1. 21-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, K.: "Cytokine-independent Jak3 activation upon TCR stimulation through direct association of Jak3 and the TCR complex"J.Biol.Chem.. 276・27. 25378-25385 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arase, H.: "The mouse NK cell-associated antigen recognized by DX5 mAb is CD49β(α_2 integrin, VLA-2)"J.Immunol.. 167・3. 1141-1144 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi, A.: "E2A and HEB activate the pre-TCRα promoter during immature T cell development"J.Immunol.. 167・4. 2157-2163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, S.: "Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell recepor signaling by recruitment of inhibitory molecules"J.Biol.Chem.. 276・48. 45175-45183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itoh, K.: "Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP5O-ERM assembly"J.Immunol.. 168・2. 541-544 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azeredo da Silveira, S.: "Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody"J.Exp.Med.. 195・6. 665-672 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ioan-Facsinay, A.: "FcγRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses and protection from bacterial infection"Immunity. 16・3. 391-402 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokosuka, T.: "Predominant role of T cell receptor α chain in forming preimmune TCR repertoire revealed by clonal TCR reconstitution system"J.Exp.Med.. 195・8. 991-1001 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murata, Y: "The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowl disease in Janus family tyrosine kinase 3-/-and IL-2Rγ-/-mice"Int.Immunol.. 14・6. 627-636 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Redegeld, F.A.: "Immunoglobulin free light chains elicit immediate hypersensitivity-like responses"Nat.Med.. 8・7. 694-701 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Snell, D.C.: "Differential effects of reduced glycoprotein VI levels on activation of murine platelets by glycoprotein VI ligands"Biochem.J.. 368・Pt1. 293-300 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tarzi, R.M.: "Nephrotoxic nephritis is mediated by Fcg receptors on circulating leukocytes and not intrinsic renal cells"Kidney Int.. 62・6. 2087-2096 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto, K.: "Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL lpr mice"Arthritis.Rheum.. 48・2. 486-494 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, S.: "Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells"Moll.Cell.Biol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arase, N.: "IgE-mediated activation of NK cells through FcγRIII."J Immunol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito, T.: "Negative feedback of T cell activation through inhibitory adaptors and co-stimulatory receptors"Immunol.Rev.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aiase, H.: "Negative regulation of expression and function of FcγrRIII by CD3ζin murine NK cells"J. Immunol.. 166(1). 21-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomita, K: "Cytokine-independent Jak3 activation upon TCR stimulation through direct association of Jak3 and the TCR complex"J. Biol, Chem.. 276(27). 25378-25385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arase. H: "The mouse NK cell-associated antigen recognized by DX5 mAb is CD49β (α_2 integrin, VLA-2)"J. Immunol.. 167(3). 1141-1144 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi, A: "E2A and HEB activate the pre-TCRα promoter during immature T cell development"J. Immunol.. 167(4). 2157-2163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, S: "Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell recepor signaling by recruitment of inhibitory molecules"J. Biol Chem.. 276(48). 45175-5183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itoh, K: "Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly"J. Immunol.. 168(2). 541-544 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azeredo da Silveira, S: "Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high-affinity anti-erythrocyte autoantibody"J. Exp. Med.. 195(6). 665-672 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] loan-Facsinay, A: "FcγRI(CD64) contributes substantially to severity of arthritis, hypersensitivity responses and protection from bacterial infection"Immunity. 16(3). 391-402 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokosuka, T: "Predominant role of TCRα chain in forming pre-immune TCR repertoire revealed by clonal TCR reconstitution system"J. Exp, Med.. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murata, Y: "The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowl disease in Janus family tyrosine kinase 3-/- and IL-2Rγ-/- mice"Int. Immunol. 14. 627-636 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Redegeld, F A: "Immunoglobulin free light chains elicit immediate hypersensitivity-like responses"Nat. Med.. 8. 694-701 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Snell, D. C.: "Differential effects of reduced glycoprotein VI levels on activation of murine platelets by glycoprotein VI ligands"Biochem. J.. 368. 293-300 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tarzi, R.M.: "Nephrotoxic nephritis is mediated by Feγ receptors on circulating leukocytes and not intrinsic renal cells"Kidney Int.. 62. 2087-2096 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto, K.: "Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL lpr mice"Arthritis Rheum.. 48. 486-494 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, S.: "Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells"Moll. Cell. Biol.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arase, N.: "IgE-mediated activation of NK cells through FcγRlll"J. Immunol.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito, T.: "Negative feedback of T cell activation through inhibitory adaptors and co-stimulatory receptors"Immunol Rev.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itoh, K.: "Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP5O-ERM assembly"J.Immunol.. 168・2. 541-544 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Azeredo da Silveira, S.: "Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody"J.Exp.Med.. 195・6. 665-672 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ioan-Facsinay, A.: "Fc_γRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses and protection from bacterial infection"Immunity. 16・3. 391-402 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yokosuka, T.: "Predominant role of T cell receptor α chain in forming preimmune TCR repertoire revealed by clonal TCR reconstitution system"J.Exp.Med.. 195・8. 991-1001 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata, Y.: "The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowl disease in Janus family tyrosine kinase 3-/-and IL-2R_γ-/-mice"Int.Immunol.. 14・6. 627-636 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Redegeld, F.A.: "Immunoglobulin free light chains elicit immediate hypersensitivity-like responses"Nat.Med.. 8・7. 694-701 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Snell, D.C: "Differential effects of reduced glycoprotein VI levels on activation of murine platelets by glycoprotein VI ligands"Biochem.J.. 368・Pt1. 293-300 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tarzi, R.M.: "Nephrotoxic nephritis is mediated by Fc_γ receptors on circulating leukocytes and not intrinsic renal cells"Kidney Int.. 62・6. 2087-2096 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsumoto, K.: "Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL lpr mice"Arthritis.Rheum.. 48・2. 486-494 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamasaki, S: "Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells"Moll.Cell.Biol.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Arase, N.: "IgE-mediated activation of NK cells through Fc_γRIII"J.Immunol.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito, T.: "Negative feedback of T cell activation through inhibitory adaptors and co-stimulatory receptors"Immunol.Rev.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Arase, H.: "Negative regulation of expression and function of Fcγ RIII by CD3ζ in murine NK cells"J.Immunol. 166・1. 21-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomita, K.: "Cytokine-independent Jak3 activation upon TCR stimulation through direct association of Jak3 and the TCR complex"J.Biol.Chem.. 276・27. 25378-25385 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arase, H.: "The mouse NK cell-associated antigen recognized by DX5 mAb is CD49β(α,integrin,VLA-2)"J.Immunol.. 167・3. 1141-1144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi, A.: "E2A and HEB activate the pre-TCRα promoter during immature T cell development"J.Immunol.. 167・4. 2157-2163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamasaki, S.: "Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell recepor signaling by recruitment of inhibitory molecules"J.Biol.Chem.. 276・48. 45175-45183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh, K.: "Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly"J.Immunol.. 168・2. 541-544 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Azeredo da Silveira, S.: "Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high-affinity anti-erythrocyte autoantibody"J.Exp.Med.. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ioan-Facsinay, A.: "Fcγ RI(CD64)contributes substantially to severity of arthritis,hypersensitivity responses and protection from bacterial infection"Immunity. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokosuka, T.: "Predominant role of TCRα chain in forming pre-immune TCR repertoire revealed by clonal TCR reconstitution system"J.Exp.Med.. (In press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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