ICOS is critical for CD40-mediated antibody class switching

Alexander J. McAdam, Rebecca J. Greenwald, Michele A. Levin, Tatyana Chernova, Nelly Malenkovich, Vincent Ling, Gordon J. Freeman and Arlene H. Sharpe ()
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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

Nature, 2001, vol. 409, issue 6816, 102-105

Abstract: 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.

Date: 2001
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DOI: 10.1038/35051107

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