PERSPECTIVE n engl j med 10.1056/nejmp068087 duction of interleukin-2 and other cytokines, up-regulate cell-survival genes (such as Bcl-xL), promote energy metabolism (glucose uptake and rate of glycolysis), and facilitate cell-cycle progression. The effects of the binding of B7 to CD28 can be mimicked by cross-linking antibodies directed against this receptor. Most of the antibodies that have been developed against CD28 in mice and humans have no biologic effects on their own but are potent costimulators when given with antigen or mimics of antigen. There is one notable exception, however: an anti-CD28 antibody, called a superagonistic antibody, activates T cells in the apparent absence of the overt engagement of the antigen receptor. 2 The basis for this unusual action and its physiological implications are not clearly defined, but it may involve amplification of tonic T-cell–receptor signals.

B7–CD28 signals also play a critical role in the development and survival of a class of T cells called regulatory T cells, whose function is to inhibit immune responses and maintain self-tolerance. The fundamental importance of regulatory T cells in immune regulation, together with