ICOS is essential for effective T-helper-cell responses

The outcome of T-cell responses after T-cell encounter with specific antige ns is modulated by co-stimulatory signals, which are required for both lymp hocyte activation and development of adaptive immunity(1-3). ICOS4,5, an in ducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. IC OS binds specifically to its counter-receptor B7RP-1 (refs 5-7), 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 be tween T and B cells and for normal antibody responses to T-cell-dependent a ntigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS re sults in severely deficient T-cell-dependent B-cell responses. Germinal cen tre formation is impaired and immunoglobulin class switching, including pro duction of allergy-mediating IgE, is defective. ICOS-deficient T cells prim ed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interfer on-gamma.