title: Decreased IL-7 responsiveness is related to oxidative stress in HIV disease.
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.
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Magdalina
authors.initials: M
authors.lastname: Kalinowska
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bazdar
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Funderburg
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000097:blood; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D050799:STAT5 Transcription Factor; C000820:semidehydroascorbic acid; D006861:Hydrogen Peroxide; D003683:Dehydroascorbic Acid