T-cell co-stimulation through B7RP-1 and ICOS

T-cell activation requires co-stimulation through receptors such as CD28 (r efs 1-3) and antigen-specific signalling through the T-cell antigen recepto r. Here we describe a new murine costimulatory receptor-ligand pair. The re ceptor, which is related to CD28 and is the homologue of the human protein ICOS4, is expressed on activated T cells and resting memory T cells. The li gand, which has homology to B7 molecules and is called B7-related protein-1 (B7RP-1), is expressed on B cells and macrophages. ICOS and B7RP-1 do not interact with proteins in the CD28-B7 pathway, and B7RP-1 co-stimulates T c ells in vitro independently of CD28. Transgenic mice expressing a B7RP-1-Fc fusion protein show lymphoid hyperplasia in the spleen, lymph nodes and Pe yer's patches. Presensitized mice treated with B7RP-1-Fc during antigen cha llenge show enhanced hypersensitivity. Therefore, B7RP-1 exhibits co-stimul atory activities in vitro and in vivo. ICOS and B7RP-1 define a new and dis tinct receptor-ligand pair that is structurally related to CD28-B7 and is i nvolved in the adaptive immune response.