Human and Murine Immune Thrombocytopenia (ITP) Is Associated with a Peripheral Deficiency of CD4- T Regulatory Cells (Tc-regs)

Abstract 3333

CD8+ T suppressor cells were originally described by Gershon on Kondo more than 40 years ago, however, because of difficulties in their characterization, they fell out of favor for decades. T suppression was resurrected by the discovery of CD4+ CD25+ FoxP3+ T regulatory cells as being the critical cell in the maintenance of self tolerance. Recently, a non-conventional CD4-CD25+FoxP3+ T cell subset termed Tc regulatory cells (Tc-regs) has been described that are also important in inducing tolerance against self. A peripheral CD4+ Treg deficiency has been suggested to be the potential cause of ITP, however, the role of this newly described CD4- T cell population has not been determined. To address the role of these cells, we studied lymphocyte responses in 36 patients with ITP (18 newly-diagnosed and 18 in remission) and a murine model of ITP. Peripheral blood mononuclear cells from patients or spleens and thymi from mice were isolated and FoxP3 expressing Tc-regs were evaluated by flow cytometry. Results show that compared with healthy control subjects, the percentages of peripheral Tc-regs in newly diagnosed patients with ITP were significantly decreased. The Tc-reg deficiency was rescued in those patients in remission due to therapy. Similar results were observed in an active model of murine ITP. Additionally, the murine model of ITP revealed that the CD4- deficient population expressed CD8. These results suggest that, like CD4+ T regs, there is a significant reduction in peripheral Tc-regs in both human and murine ITP and disease remission correlates with rescuing the deficiency.