Decreased IL-7 responsiveness is related to oxidative stress in HIV disease

PLoS One. 2013;8(3):e58764. doi: 10.1371/journal.pone.0058764. Epub 2013 Mar 7.

Abstract

HIV disease results in decreased IL-7 receptor expression and IL-7 responsiveness in T cells. To explore mechanisms of these deficiencies, we compared CD127 expression and IL-7 induction of P-STAT5 in T cells from HIV-infected persons with serum concentrations of cytokines (IL-7, IL-6 and IL-15), markers of microbial translocation (sCD14 and LPS), and with an indicator of oxidative stress (malondialdehyde (MDA) adducts). CD127 expression was directly related to IL-7 responsiveness in most CD8+ T cell subsets but not in CD4+ T cells from HIV-infected persons. MDA adducts were increased in serum of HIV-infected patients and were inversely related to IL-7 responsiveness in CD8+ T cells and in central memory CD4+ T cells. Incubation of T cells from healthy controls with hydrogen peroxide resulted in impairments in IL-7 induction of P-STAT5. These findings suggest that oxidative stress that is characteristic of HIV disease could contribute to impairments in IL-7 responsiveness and disrupt T cell homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Dehydroascorbic Acid / analogs & derivatives
  • Dehydroascorbic Acid / blood
  • HIV Infections / immunology*
  • HIV Infections / metabolism*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Interleukin-7 / metabolism*
  • Interleukin-7 / pharmacology
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Middle Aged
  • Oxidative Stress*
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit
  • STAT5 Transcription Factor
  • semidehydroascorbic acid
  • Hydrogen Peroxide
  • Dehydroascorbic Acid