ICOS is essential for effective T-helper-cell responses

Anna Tafuri, Arda Shahinian, Friedhelm Bladt, Steve K. Yoshinaga, Manel Jordana, Andrew Wakeham, Louis-Martin Boucher, Denis Bouchard, Vera S. F. Chan, Gordon Duncan, Bernhard Odermatt, Alexandra Ho, Annick Itie, Tom Horan, John S. Whoriskey, Tony Pawson, Josef M. Penninger, Pamela S. Ohashi and Tak W. Mak ()
Additional contact information
Anna Tafuri: Amgen Institute
Arda Shahinian: Amgen Institute
Friedhelm Bladt: Mount Sinai Hospital, Samuel Lunenfeld Research Institute
Steve K. Yoshinaga: Amgen
Manel Jordana: Faculty of Health Science, McMaster University
Andrew Wakeham: Amgen Institute
Louis-Martin Boucher: Amgen Institute
Denis Bouchard: Amgen Institute
Vera S. F. Chan: Ontario Cancer Institute, University of Toronto
Gordon Duncan: Amgen Institute
Bernhard Odermatt: University Hospital Zurich
Alexandra Ho: Amgen Institute
Annick Itie: Amgen Institute
Tom Horan: Amgen
John S. Whoriskey: Amgen
Tony Pawson: Mount Sinai Hospital, Samuel Lunenfeld Research Institute
Josef M. Penninger: Amgen Institute
Pamela S. Ohashi: Ontario Cancer Institute, University of Toronto
Tak W. Mak: Amgen Institute

Nature, 2001, vol. 409, issue 6816, 105-109

Abstract: 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 immunity1,2,3. ICOS4,5, 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.

Date: 2001
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DOI: 10.1038/35051113

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