Co-stimulation and co-inhibition: equal partners in regulation

Specific immune responses are controlled by two counterbalancing mechanisms-co-stimulation and co-inhibition. Antigen receptors determine specificity, activate co-stimulation and/or co-inhibition, and interact with these co-stimulatory/co-inhibitory mechanisms to dictate the direction of the immune response, either positive or negative. Co-stimulatory or co-inhibitory ligands interact with their specific receptors and may indicate the context in which antigen is perceived by lymphocytes. Ligation of antigen receptors may activate only co-stimulatory or co-inhibitory mechanisms, and thus may influence secondarily the direction of the immune response. Furthermore, the activity of a given co-stimulator or co-inhibitory receptor is modified depending on signalling via the antigen receptor. If neither co-stimulators nor co-inhibitors are present, lymphocytes, activated in response to antigen receptor signalling, produce low levels of effector elements and then revert to inactivity. Co-inhibitors are defective in autoimmune disease.