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. 2001 Jan 4;409(6816):105-9.
doi: 10.1038/35051113.

ICOS is essential for effective T-helper-cell responses

A Tafuri  1 , A Shahinian, F Bladt, S K Yoshinaga, M Jordana, A Wakeham, L M Boucher, D Bouchard, V S Chan, G Duncan, B Odermatt, A Ho, A Itie, T Horan, J S Whoriskey, T Pawson, J M Penninger, P S Ohashi, T W Mak
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ICOS is essential for effective T-helper-cell responses

A Tafuri et al. Nature. .

Abstract

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-gamma.

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