Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells

Stem Cells. 2006 Feb;24(2):386-98. doi: 10.1634/stemcells.2005-0008. Epub 2005 Aug 25.


Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-gamma produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-gamma. The suppressive effect of IFN-gamma was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell- derived IFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B-Lymphocytes / physiology
  • Bone Marrow Cells / physiology*
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Proliferation*
  • Cells, Cultured
  • Drug Synergism
  • Humans
  • Immunologic Factors / pharmacology
  • Immunophenotyping
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma / pharmacology*
  • Killer Cells, Natural / physiology
  • Lymphocyte Activation
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocytes / physiology
  • Time Factors


  • CD4 Antigens
  • CD8 Antigens
  • Immunologic Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Receptors, Interleukin-2
  • Interferon-gamma