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

R Khattri, T Cox, SA Yasayko, F Ramsdell - Nature immunology, 2003 - nature.com
R Khattri, T Cox, SA Yasayko, F Ramsdell
Nature immunology, 2003nature.com
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 TR cells and is associated with TR cell activity and phenotype.
Scurfin-deficient mice lack TR cells, whereas mice that overexpress Foxp3 possess more TR …
Abstract
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 TR cells and is associated with TR cell activity and phenotype. Scurfin-deficient mice lack TR cells, whereas mice that overexpress Foxp3 possess more TR cells. In Foxp3-overexpressing mice, both CD4+CD25 and CD4CD8+ 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 TR cell lineage.
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