Costimulatory Pathways: Physiology and Potential Therapeutic Manipulation in Systemic Lupus Erythematosus

Figure 1

Expression of costimulation molecules in different stages of immune activation and their concerted effector functions. (a) Initial phase of immune activation; (b) maximal phase of immune activation with expression of many costimulatory molecules (figure is for depiction only, costimulation molecules may not be all expressed in a single immune reaction), coupled with proliferation and differentiation of immunocytes, production of proinflammatory cytokines and autoantibodies; (c) after reaching the peak of activation, CTLA4 expressed on T cells interacts with CD80/86 on B cells/APCs with higher affinity than CD28. Immune response attenuates and costimulatory pathways start to disintegrate. CD28 molecules expressed during maximal activation phase are endocytosed, pictorially depicted as intracellular small round yellow vesicles in the T cells of condition (c). Abbreviations: TCR: T-cell receptor; MHC II: class II major histocompatibility complex; APC: antigen-presenting cells; and autoAb: autoantibodies.