Co‐Stimulation and Co‐Inhibition: Equal Partners in Regulation

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Abstract
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.

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