Cutting edge: The related molecules CD28 and inducible costimulator deliver both unique and complementary signals required for optimal T cell activation

Optimal T cell activation requires engagement of CD28 with its counterligan ds B7-1 and B7-2, Inducible costimulator (ICOS) is the third member of the CD28/CTLA4 family that binds a B7-like protein, B7RP-1. Administration of I COS-Ig attenuates T cell expansion following superantigen (SAg) administrat ion, but fails to regulate either peripheral deletion or anergy induction. ICOS-Ig, but not CTLA4-Ig, uniquely regulates SAg-induced TNF-alpha product ion, whereas IL-2 secretion is modulated by CTLA4-Ig, but not ICOS-Ig. In c ontrast, both ICOS and CD28 are required for complete attenuation of IL-4 p roduction. Our data suggest that ICOS and CD28 regulate T cell expansion an d that ligation of either CD28 or ICOS can either uniquely regulate cytokin e production (IL-2/TNF-alpha) or synergize for optimal cytokine production (IL-4) after SAg administration.