Basic science for the clinician 32: T-cells with regulatory function

Tolerance is one of the major requirements of a successful immune system: destroy invaders but recognize self and the benign environment to leave them alone. Central tolerance is achieved by deletion of T-cells with T-cell antigen receptors that recognize self-antigens too well. However, within the population of T-cells that actually survive the harrowing experience of passage through the thymus (wherein over 98% of all pre-T-cells perish), there persist T-cells capable of inducing autoimmune damage. How then to avoid autoaggression? One theory in the 1970s was that there were peripheral T-suppressor cells that actively dampened these autoimmune proclivities. One problem presented itself, however; despite the fact that such an immunologic activity could be measured, no one could identify the cells that mediated the activity and so the concept fell into disfavor. However, the concept of peripheral regulation by a distinct (at last identifiable!) population of T-cells is now back in vogue. These T-regulatory (T-reg) cells have an important function in immune homeostasis. T-reg demand our attention as we try to manipulate the molecular biology of immune responses and inflammation to control autoimmune disorders and enhance transplantation efficiency.