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CD47 signals T cell death.

R D Pettersen1, K Hestdal, M K Olafsen

  • 1Department of Pediatric Research, The National Hospital, Oslo, Norway. rolf.pettersen@klinmed.uio.no

Journal of Immunology (Baltimore, Md. : 1950)
|June 8, 1999
PubMed
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Activation of the CD47 receptor rapidly induces T cell apoptosis through a novel pathway, independent of Fas or TNF signaling. This finding suggests CD47 plays a critical role in controlling activated T cell populations.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • T cell activation-induced death is crucial for immune regulation.
  • Fas and TNF receptor ligation are known inducers of T cell apoptosis.
  • The role of other receptors in T cell death signaling remains less understood.

Purpose of the Study:

  • To investigate the role of CD47 receptor activation in T cell apoptosis.
  • To identify novel pathways involved in T cell death signaling.

Main Methods:

  • Utilized a novel monoclonal antibody (mAb), Ad22, targeting a specific epitope on CD47.
  • Assessed T cell apoptosis in Jurkat cells and peripheral blood mononuclear cells (PBMCs) using morphological changes, phosphatidylserine exposure, propidium iodide uptake, and flow cytometry.
  • Investigated CD47-mediated cell death in T cell lines deficient in CD3, CD4, CD45, or p56lck signaling pathways.

Related Experiment Videos

  • Examined the involvement of Fas, TNF receptor signaling, DNA fragmentation, and caspase-like proteases.

    • Main Results:

    • Activation of a specific CD47 epitope by mAb Ad22 rapidly induced apoptosis in Jurkat cells and CD3epsilon-stimulated PBMCs.
    • Apoptosis was not induced by mAbs targeting different CD47 regions (2D3, B6H12).
    • CD47-mediated T cell death was independent of CD3, CD4, CD45, or p56lck.
    • Coligation of CD3epsilon and CD47 enhanced apoptosis in CD3-functional Jurkat cells.
    • Normal T cells required preactivation to undergo CD47-induced apoptosis.
    • The observed T cell death was independent of Fas/TNF signaling and did not involve DNA fragmentation or typical caspase pathways.

    Conclusions:

    • Specific activation of CD47 can rapidly induce T cell apoptosis via a novel pathway.
    • This CD47-mediated cell death mechanism is distinct from Fas/TNF-induced apoptosis.
    • CD47 may play a significant role in regulating the survival of activated T cells.