Regulation of T and B cell responses by modulating interactions between CD28/CTLA4 and their ligands, CD80 and CD86.

In recent years, it has become clear that the fate of lymphocyte interactions with antigen is determined not only by signals through antigen-specific receptors, but by interactions between pairs of accessory molecules. One such crucial pair of ligands is that between CD80/CD86, expressed by professional APCs and activated T and B cells, and CD28 (resting and activated T cells primarily) and CTLA4 (activated T cells). Signals in this system can amplify (CD28) or inhibit (CTLA4) T cell responses. The uses of soluble competitors for CD28 (CTLA4-Ig) and agonists for the inhibitory receptor CTLA4 (CD80-Ig) offer therapeutic possibilities to tailor autoimmune responses in nonpathogenic directions.