An Essential Role for Scurfin in CD4+CD25+ T Regulatory Cells

Nat Immunol. 2003 Apr;4(4):337-42. doi: 10.1038/ni909. Epub 2003 Mar 3.

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