Cutting edge: OX40 inhibits TGF-beta- and antigen-driven conversion of naive CD4 T cells into CD25+Foxp3+ T cells

J Immunol. 2007 Aug 1;179(3):1427-30. doi: 10.4049/jimmunol.179.3.1427.

Abstract

Naive CD4 T cells can develop into regulatory T cells by acquiring the transcription factor Foxp3. Combined signals from the TCR, CD28, IL-2R, and TGF-beta R promote Foxp3 expression in activated naive CD25(-) CD4 T cells. Here we show that OX40 (CD134) signaling inhibits TGF-beta-driven Foxp3 mRNA and suppresses the conversion of naive Ag-specific transgenic CD4 T cells into CD25(+)Foxp3(+) T cells. These data identify OX40 as a negative regulator of Foxp3 and suggest that OX40 can concomitantly promote effector T cell generation while antagonizing the differentiation of adaptive Foxp3(+) regulatory T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens / physiology*
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Forkhead Transcription Factors / antagonists & inhibitors
  • Forkhead Transcription Factors / biosynthesis
  • Growth Inhibitors / physiology*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, OX40 / physiology*
  • Resting Phase, Cell Cycle / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / physiology

Substances

  • Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Growth Inhibitors
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, OX40
  • Tnfrsf4 protein, mouse
  • Transforming Growth Factor beta