Costimulatory signals controlling regulatory T cells.

T he concept of specialized suppressor T cells (now commonly called regulatory T cells or Tregs), which was abandoned by most immunologists in the early 1980s (1), was rescued by the description of a marker for their identification and isolation by Sakaguchi et al. (2), who, in 1995, described a CD4 CD25 subpopulation of T cells that could prevent pathology in a mouse autoimmune disease model. However, the marker CD25, the -chain of the high-affinity IL-2 receptor, is also induced on conventional T cells after activation. The dilemma arose as to how one could distinguish genuine Tregs from recently activated conventional T cells. Furthermore, the suppressor activity of CD4 CD25 Tregs in vitro depended on their prior stimulation and could be overcome by strong costimulation (3, 4). What were the signals that controlled the activity of CD4 CD25 Tregs in vivo that allowed them to inhibit certain immune responses but not others?