Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4(+)CD25(+) regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4(+)CD25(hi) Tregs. We found a comparable frequency of circulating CD4(+)CD25(hi)Foxp3(+) Tregs in patients and controls (n = 16, P > .05). However, sorted CD4(+)CD25(hi) cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by crossmixing experiments with Tcells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP.