Activated T cells express the OX40 ligand: requirements for induction and costimulatory function

Immunology. 2006 Feb;117(2):196-204. doi: 10.1111/j.1365-2567.2005.02279.x.


OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T-cell activation. OX40 expression is transiently up-regulated on T cells following T-cell receptor engagement, while OX40L is expressed on antigen-presenting cells following activation. Although expression of the OX40L by T cells has been reported, the requirements for induction of OX40L on T cells have not been studied in detail. Here, we demonstrate that the OX40L can be induced on murine CD4(+) and CD8(+) T cells after 6 days of culture under T helper type 1 (Th1) conditions, but not under Th2 conditions. Induction of OX40L expression required a high concentration of interleukin-12 (IL-12), was not seen in the presence of interferon-gamma, and was dependent on signal transducer and activator of transcription type 4 (STAT4). Notably, induction of OX40L on T cells was only seen at very low concentrations of antigen or anti-CD3. T-cell-expressed OX40L was fully capable of delivering a potent costimulatory signal that enhanced the proliferation of CD4(+) T cells as well as promoted their differentiation to Th2 cells. OX40L expression could also be induced on CD4(+) T cells in vivo following immunization with low-dose antigen and an IL-12 inducer. OX40/OX40L interactions between antigen-specific T cells may occur in T-cell zones in lymph node and spleen when OX40L expression has diminished on APC. Costimulation by T-cell-expressed OX40L may result in deviation of a Th1 response to a Th2 response under conditions where T cells are exposed to low concentrations of foreign or autoantigens in the presence of high concentrations of IL-12.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • OX40 Ligand
  • STAT4 Transcription Factor / immunology
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factors / immunology
  • Tumor Necrosis Factors / metabolism*


  • Membrane Glycoproteins
  • OX40 Ligand
  • STAT4 Transcription Factor
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factors
  • Interleukin-12
  • Interferon-gamma