CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells

J Infect Dis. 2011 Dec 15;204(12):1927-35. doi: 10.1093/infdis/jir659. Epub 2011 Oct 17.

Abstract

Most patients with human immunodeficiency virus (HIV) who remain CD4(+) T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As CD4(+) T-cell activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV patients with good or poor CD4(+) T-cell recovery on long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased in CD4(+) T cells of patients with poor CD4(+) T-cell recovery, whereas levels in patients with good recovery did not differ from those in healthy controls. Poor CD4(+) T-cell recovery was also associated with CD4(+) T-cell expression of markers of activation, senescence, and apoptosis, and with increased serum levels of the lipopolysaccharide receptor and soluble CD14, but these were not significantly correlated with expression of the interferon-stimulated genes. Therefore, CD4(+) T-cell recovery may be adversely affected by the effects of IFN-α, which may be amenable to therapeutic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Apoptosis
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD57 Antigens / blood
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Cross-Sectional Studies
  • Female
  • Gene Expression / drug effects*
  • Gene Expression / genetics
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HLA-DR Antigens / blood
  • Humans
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Interferon-alpha / pharmacology*
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides / blood
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism*
  • Transcription Factors / blood
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • fas Receptor / blood

Substances

  • Anti-Retroviral Agents
  • CD57 Antigens
  • HLA-DR Antigens
  • ISG56 protein, human
  • Interferon-alpha
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • RNA, Messenger
  • Transcription Factors
  • fas Receptor