Basic science for the clinician 55: CTLA-4

In physiological systems, for every "yang," there must be a "yin," for uncontrolled systems can run amok. This is the case for the T-cell compartment of the immune system, where activation must be modulated, dampened, and ultimately reversed; to not apply the brakes leads to dire consequences. In less than 20 years, CTLA-4 has emerged from being an orphan, next becoming a physiological star with ever-emerging effects, and finally to being a therapeutic target-an impressive example of evolution and one that continues. Understanding the costimulatory effects and mechanisms of CTLA-4 and the redundancies intrinsic to costimulation is important in understanding T-cell function and dysfunction in disease. A future article in this series will describe inducible T-cell costimulator, which is a normal by-pass to CTLA-4's effects.