An essential role for Scurfin in CD4+CD25+ T regulatory cells

The molecular properties that characterize CD4(+)CD25(+) regulatory T cells (T-R cells) remain elusive. Absence of the transcription factor Scurfin (also known as forkhead box P3 and encoded by Foxp3) causes a rapidly fatal lymphoproliferative disease, similar to that seen in mice lacking cytolytic T lymphocyte-associated antigen 4 (CTLA-4). Here we show that Foxp3 is highly expressed by T-R cells and is associated with T-R cell activity and phenotype. Scurfin-deficient mice lack T-R cells, whereas mice that overexpress Foxp3 possess more T-R cells. In Foxp3-overexpressing mice, both CD4(+)CD25(-) and CD4(-)CD8(+) T cells show suppressive activity and CD4(+)CD25(-) cells express glucocorticoid-induced tumor-necrosis factor receptor-related (GITR) protein. The forced expression of Foxp3 also delays disease in CTLA-4(-/-) mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the T-R cell lineage.