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ICOS is critical for CD40-mediated antibody class switching

Author

Listed:
  • Alexander J. McAdam

    (Brigham and Women's Hospital and Harvard Medical School)

  • Rebecca J. Greenwald

    (Brigham and Women's Hospital and Harvard Medical School)

  • Michele A. Levin

    (Brigham and Women's Hospital and Harvard Medical School)

  • Tatyana Chernova

    (Dana-Farber Cancer Institute)

  • Nelly Malenkovich

    (Dana-Farber Cancer Institute)

  • Vincent Ling

    (Genetics Institute)

  • Gordon J. Freeman

    (Dana-Farber Cancer Institute)

  • Arlene H. Sharpe

    (Brigham and Women's Hospital and Harvard Medical School)

Abstract

The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in regulating T-cell differentiation1,2,3,4,5. Because co-stimulatory signals are critical for regulating T-cell activation, an understanding of co-stimulatory signals may enable the design of rational therapies for immune-mediated diseases6. According to the two-signal model for T-cell activation, T cells require an antigen-specific signal and a second, co-stimulatory, signal for optimal T-cell activation6. The co-stimulatory signal promotes T-cell proliferation, lymphokine secretion and effector function. The B7–CD28 pathway provides essential signals for T-cell activation, but does not account for all co-stimulation. We have generated mice lacking ICOS (ICOS-/-) to determine the essential functions of ICOS. Here we report that ICOS-/- mice exhibit profound deficits in immunoglobulin isotype class switching, accompanied by impaired germinal centre formation. Class switching was restored in ICOS-/- mice by CD40 stimulation, showing that ICOS promotes T-cell/B-cell collaboration through the CD40/CD40L pathway.

Suggested Citation

  • Alexander J. McAdam & Rebecca J. Greenwald & Michele A. Levin & Tatyana Chernova & Nelly Malenkovich & Vincent Ling & Gordon J. Freeman & Arlene H. Sharpe, 2001. "ICOS is critical for CD40-mediated antibody class switching," Nature, Nature, vol. 409(6816), pages 102-105, January.
    • Handle: RePEc:nat:nature:v:409:y:2001:i:6816:d:10.1038_35051107
    DOI: 10.1038/35051107
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    Cited by:

    1. Carleigh A O’Brien & Tajie H Harris, 2020. "ICOS-deficient and ICOS YF mutant mice fail to control Toxoplasma gondii infection of the brain," PLOS ONE, Public Library of Science, vol. 15(1), pages 1-16, January.

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