TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells

J Exp Med. 2005 Apr 4;201(7):1061-7. doi: 10.1084/jem.20042276.

Abstract

Transforming growth factor (TGF)-beta1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-beta1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4(+)CD25(+) regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8-10-d-old TGF-beta1-deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-beta-mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-beta1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Forkhead Transcription Factors
  • Immune Tolerance / immunology*
  • Immunosuppression
  • Mice
  • Mice, Inbred Strains
  • Receptors, Interleukin-2 / metabolism
  • Signal Transduction / immunology*
  • Thymus Gland / immunology*
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Interleukin-2
  • Transforming Growth Factor beta