Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells

Immunobiology. 2010 Jun;215(6):452-7. doi: 10.1016/j.imbio.2009.08.007. Epub 2009 Sep 17.


Pro-inflammatory cytokines like interferon-gamma (IFN-gamma) are considered to be important in the development of anaemia of chronic disease (ACD). Both, inhibitory and stimulatory activities of IFN-gamma on erythropoiesis have been observed in vitro earlier. IFN-gamma induces several biochemical pathways in human monocytes, among them neopterin formation by GTP-cyclohydrolase I (GTP-CH I) and tryptophan degradation by the enzyme indoleamine 2,3-dioxygenase (IDO). IDO-mediated tryptophan deprivation efficiently inhibits the growth of proliferating cells and microbes, thus we wanted to examine whether enhanced tryptophan degradation by monocytic precursor cells also suppresses erythropoiesis. Therefore, IFN-gamma-mediated pathways were investigated in human CD34(+) progenitor cells, and effects of IFN-gamma on the proliferative activity of different progenitor subpopulations were studied. Cells were either cultivated in agar-conditioned medium (ACM) or in medium containing erythroid growth factors interleukin-3 (IL-3) and stem cell factor (SCF; EGFCM). Stimulation of CD34(+) cells with IFN-gamma in different doses (either 5000U/ml once or 200 and 400U/ml every other day) induced tryptophan degradation and in parallel also neopterin formation. Unstimulated cells cultured with ACM produced higher amounts of neopterin and kynurenine (all p<0.05). IFN-gamma stimulated higher kynurenine and neopterin formation in cells cultivated in EGFCM, stimulation with 400U IFN-gamma every other day was most effective. IFN-gamma stimulated the growth and proliferation of CFU-E and BFU-E (3-8) in both media. In conclusion, stimulation of haematopoietic stem cells with IFN-gamma activates IDO and neopterin formation, and it also exerts an influence on the proliferation of various stem cell populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / immunology
  • Anemia / metabolism
  • Antigens, CD34*
  • Antiviral Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Erythroid Precursor Cells / enzymology*
  • Erythroid Precursor Cells / immunology
  • Erythropoiesis / drug effects*
  • Erythropoiesis / immunology
  • GTP Cyclohydrolase / immunology
  • GTP Cyclohydrolase / metabolism
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Interferon-gamma / pharmacology*
  • Monocytes / immunology
  • Neopterin / biosynthesis*
  • Neopterin / immunology
  • Tryptophan / immunology
  • Tryptophan / metabolism


  • Antigens, CD34
  • Antiviral Agents
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Neopterin
  • Interferon-gamma
  • Tryptophan
  • GTP Cyclohydrolase