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 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.
MeSH terms
-
Abatacept
-
Animals
-
Antigens, CD
-
Antigens, Differentiation / genetics
-
Antigens, Differentiation / metabolism
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism*
-
CTLA-4 Antigen
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology*
-
DNA-Binding Proteins / metabolism*
-
Forkhead Transcription Factors
-
Glucocorticoid-Induced TNFR-Related Protein
-
Immunoconjugates*
-
Interleukin-10 / metabolism
-
Mice
-
Mice, Transgenic
-
Receptors, Interleukin-2 / immunology
-
Receptors, Interleukin-2 / metabolism*
-
Receptors, Nerve Growth Factor / metabolism
-
Receptors, Tumor Necrosis Factor / metabolism
-
Transforming Growth Factor beta / metabolism
Substances
-
Antigens, CD
-
Antigens, Differentiation
-
CTLA-4 Antigen
-
CTLA4 protein, human
-
Ctla4 protein, mouse
-
DNA-Binding Proteins
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
Glucocorticoid-Induced TNFR-Related Protein
-
Immunoconjugates
-
Receptors, Interleukin-2
-
Receptors, Nerve Growth Factor
-
Receptors, Tumor Necrosis Factor
-
TNFRSF18 protein, human
-
Tnfrsf18 protein, mouse
-
Transforming Growth Factor beta
-
Interleukin-10
-
Abatacept