Interferon-gamma-mediated pathways and in vitro PBMC proliferation in HIV-infected patients

Biol Chem. 2009 Feb;390(2):115-23. doi: 10.1515/BC.2009.018.


HIV infection is characterized by progressive immunodeficiency: HIV-infected peripheral blood mononuclear cells (PBMCs) cannot properly react to stimulation with allo-antigens and mitogens. In this study, we examined interferon-gamma (IFN-gamma)-mediated pathways and the proliferative response of mitogen-stimulated HIV-infected PBMCs in vitro. PBMCs of 30 HIV-infected patients were stimulated with the mitogens concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Mitogen stimulation induced expression of IFN-gamma, GTP cyclohydrolase I (GCH-I), and indoleamine (2,3)-dioxygenase (IDO) resulting in enhanced neopterin formation and tryptophan degradation by HIV-infected and control PBMCs. IFN-gamma concentrations correlated with neopterin levels and tryptophan degradation. Proliferative responses to PHA and PWM cytokine were lower in HIV patients, with IFN-gamma formation predicting proliferative responses. Higher mRNA expression of IFN-gamma, GCH-I and IDO after 6 h was related to better proliferative responses in HIV-infected PBMCs. In conclusion, induction of IFN-gamma and subsequent enzymes appears to importantly influence the proliferative response of HIV-infected PBMCs in vitro, suggesting a prominent role of the cytokine in the development of immunodeficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • HIV Infections*
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / drug effects
  • Male
  • Mitogens / pharmacology
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • Reference Standards
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction


  • Mitogens
  • RNA, Messenger
  • Interferon-gamma