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.