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Related Experiment Videos

CD38 is functionally dependent on the TCR/CD3 complex in human T cells

M Morra1, M Zubiaur, C Terhorst

  • 1Department of Genetics, Biology and Medical Chemistry, and Postgraduate School of Clinical Pathology, University of Torino Medical School, Italy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 12, 1998
PubMed
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Surface CD38 signaling is linked to the T cell receptor (TCR)/CD3 complex, not independent. This interaction influences calcium mobilization, T cell death, and costimulation, highlighting a crucial functional interdependence.

Area of Science:

  • Immunology
  • Cell Signaling

Background:

  • Surface CD38 plays a role in T cell activation through cytoplasmic substrate phosphorylation and calcium mobilization.
  • The precise signaling pathway of CD38, whether independent or linked to the TCR/CD3 complex, remains to be fully elucidated.

Purpose of the Study:

  • To investigate whether CD38-mediated signaling operates independently or is integrated with the TCR/CD3 signaling machinery.
  • To analyze the functional consequences of CD38 activation on T cell phenotype and growth.

Main Methods:

  • Utilized the agonistic IB4 monoclonal antibody (mAb) to stimulate CD38.
  • Monitored cytoplasmic calcium (Ca2+) levels and PLC-gamma1 phosphorylation.
  • Assessed phenotypic and functional changes in T cell growth, including apoptosis and Fas molecule expression.

Related Experiment Videos

  • Examined signaling in Jurkat cells, including mutant lines lacking CD3 structures.

    • Main Results:

    • IB4 mAb induced cytoplasmic Ca2+ increases and PLC-gamma1 phosphorylation, effects blocked by PMA.
    • CD38-mediated signaling required a functional TCR/CD3 complex, as evidenced by the lack of effect in mutant cells.
    • CD38 signaling promoted T cell apoptosis, up-regulated Fas, and was inhibited by cyclosporin A.
    • The costimulatory molecule CD28 synergized with CD38 to enhance T cell apoptosis.

    Conclusions:

    • CD38 signaling is functionally interdependent with the TCR/CD3 signaling pathway.
    • CD38 activation influences key T cell processes, including calcium flux, apoptosis, and costimulation.
    • The findings reveal a significant integration between CD38 and TCR/CD3 signaling networks in T cells.