Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation

Blood. 2004 Jun 15;103(12):4619-21. doi: 10.1182/blood-2003-11-3909. Epub 2004 Mar 4.


Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN-gamma. MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology*
  • Cells, Cultured
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma / pharmacology
  • Lymphocyte Activation
  • Stromal Cells / drug effects
  • Stromal Cells / enzymology
  • Stromal Cells / immunology*
  • T-Lymphocytes / immunology*
  • Tryptophan / metabolism
  • Tryptophan Oxygenase / genetics*
  • Tryptophan Oxygenase / metabolism


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma
  • Tryptophan
  • Tryptophan Oxygenase