ICOS co-stimulatory receptor is essential for T-cell activation and function

T-lymphocyte activation and immune function are regulated by co-stimulatory molecules. CD28, a receptor for B7 gene products, has a chief role in init iating T-cell immune responses(1,2). CTLA4, which binds B7 with a higher af finity, is induced after T-cell activation and is involved in downregulatin g T-cell responses(3,4). The inducible co-stimulatory molecule (ICOS), a th ird member of the CD28/CTLA4 family, is expressed on activated T cells(5,6) . Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues a fter injection of lipopolysaccharide into animals(6,7). To understand the r ole of ICOS in T-cell activation and function, we generated and analysed IC OS-deficient mice. Here we show that T-cell activation and proliferation ar e defective in the absence of ICOS. In addition, ICOS-/- T cells fail to pr oduce interleukin-4 when differentiated in vitro or when primed in vivo. IC OS is required for humoral immune responses after immunization with several antigens. ICOS-/- mice showed greatly enhanced susceptibility to experimen tal autoimmune encephalomyelitis, indicating that ICOS has a protective rol e in inflammatory autoimmune diseases.