Sanjay D. Khare

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

T-cell activation requires co-stimulation through receptors such as CD28 (refs 1,2,3) and antigen-specific signalling through the T-cell antigen receptor. Here we describe a new murine co-stimulatory receptor–ligand pair. The receptor, which is related to CD28 and is the homologue of the human protein ICOS, is expressed on activated T cells and resting memory T cells. The ligand, 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 cells in vitro independently of CD28. Transgenic mice expressing a B7RP-1–Fc fusion protein show lymphoid hyperplasia in the spleen, lymph nodes and Peyers patches. Presensitized mice treated with B7RP-1–Fc during antigen challenge show enhanced hypersensitivity. Therefore, B7RP-1 exhibits co-stimulatory activities in vitro and in vivo. ICOS and B7RP-1 define a new and distinct receptor–ligand pair that is structurally related to CD28–B7 and is involved in the adaptive immune response.

The role of TALL-1 and APRIL in immune regulation

Abstract Members of the tumor necrosis factor (TNF) superfamily play important roles in cell proliferation and death during immune regulation. Most members are synthesized as type II transmembrane proteins; the carboxy terminal extracellular domain can be cleaved from the cell membrane to form soluble active cytokines that bind to appropriate members of the TNF receptor family. Here, we describe the biological significance of recently discovered members of the TNF superfamily (TALL-1 and APRIL) and their receptors (TACI and BCMA) in the pathophysiology of human diseases.