An essential role for Scurfin in CD4+CD25+ T regulatory cells.
The molecular properties that characterize CD4+CD25+ regulatory T cells (TR 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.
Khattri
Roli
R
Celltech R&D Inc., 1631 220th Street SE, Bothell, Washington 98021, USA.
Cox
Tom
T
Yasayko
Sue-Ann
SA
Ramsdell
Fred
F
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D018796:Immunoconjugates; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C106544:Tnfrsf18 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000069594:Abatacept