The Regulatory T Cell Family: Distinct Subsets and their Interrelations

Abstract

The idea of a naturally occurring T cell subset with suppressive function that limits the outcome of autoimmune responses was first described in the 1970s by Gershon (1). However, at that time neither the cells nor the hypothetical soluble suppressor factors responsible for the observed effects were characterized, and several inconsistencies discredited the whole concept for a long period of time. This conception was revived by studies showing that a subset of peripheral CD4⁺ T cells, which coexpress the IL-2R α-chain (CD25), is critical for the control of autoreactive T cells in vivo (2). Mice, thymectomized before day 3 after birth, lack this population of resident CD4⁺CD25⁺ cells, resulting in the development of various autoimmune diseases (3). Furthermore, depletion of CD25⁺ T cells in adult mice results also in the development of various autoimmune diseases, such as gastritis and thyroiditis (2). Subsequent in vitro studies showed that this population, now referred to as CD4⁺CD25⁺ T regulatory cells, is both anergic and suppressive (4, 5, 6).