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ICOS Is Essential For Effective T-helper-cell Responses

A. Tafuri, A. Shahinian, F. Bladt, S. Yoshinaga, M. Jordana, A. Wakeham, L. Boucher, D. Bouchard, V. Chan, G. Duncan, B. Odermatt, A. Ho, A. Itié, T. Horan, J. Whoriskey, T. Pawson, J. Penninger, P. Ohashi, T. Mak
Published 2001 · Biology, Medicine

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The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-γ.
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