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.
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Acknowledgements
This work was supported by grants from Genetics Institute (to A.H.S.) and the NIH (to A.J.M., R.J.G., G.J.F. and A.H.S.). We thank M. Collins for thoughtful discussions, and L. Du, J. Burgess and B. Chang for technical support.
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McAdam, A., Greenwald, R., Levin, M. et al. ICOS is critical for CD40-mediated antibody class switching. Nature 409, 102–105 (2001). https://doi.org/10.1038/35051107
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DOI: https://doi.org/10.1038/35051107