First Author | McAdam AJ | Year | 2001 |
Journal | Nature | Volume | 409 |
Issue | 6816 | Pages | 102-5 |
PubMed ID | 11343122 | Mgi Jnum | J:87124 |
Mgi Id | MGI:2683576 | Doi | 10.1038/35051107 |
Citation | McAdam AJ, et al. (2001) ICOS is critical for CD40-mediated antibody class switching. Nature 409(6816):102-5 |
abstractText | The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in regulating T-cell differentiation. 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 diseases. 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 activation. 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. |