title: Modulation of LPS-induced CD4+ T-cell activation and apoptosis by antioxidants in untreated asymptomatic HIV infected participants: an in vitro study.
abstract: Persistent immune activation characterises HIV infection and is associated with depletion of CD4+ T-cells and increased risk of disease progression. Early loss of gut mucosal integrity results in the translocation of microbial products such as lipopolysaccharide (LPS) into the systemic circulation. This is an important source of on-going immune stimulation. The purpose of this study was to determine levels of CD4+ T-cell activation (%CD25 expression) and apoptosis (% annexin V/7-AAD) in asymptomatic, untreated HIV infection at baseline and after stimulation with LPS and incubation with or without vitamin C and N-acetylcysteine. LPS induced a significant (P < 0.03) increase in %CD25 expression, annexin V, and 7-AAD in HIV positive individuals. NAC in combination with vitamin C, significantly (P = 0.0018) reduced activation and early apoptosis of CD4+ T-cells to a greater degree than with either antioxidant alone. Certain combinations of antioxidants could be important in reducing the harmful effects of chronic immune activation and thereby limit CD4+ T-cell depletion. Importantly, we showed that CD4+ T-cells of the HIV positive group responded better to a combination of the antioxidants at this stage than those of the controls. Therefore, appropriate intervention at this asymptomatic stage could rescue the cells before repetitive activation results in the death of CD4+ T-cells.
authors.affiliation: Haematology Division, Department of Pathology, Faculty of Medicine and Health Science, Stellenbosch University, P.O. Box 19063, Tygerberg, Cape Town 7505, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Mburu
authors.affiliation: Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa.
authors.forename: J L
authors.initials: JL
authors.lastname: Marnewick
authors.affiliation: Haematology Division, Department of Pathology, Faculty of Medicine and Health Science, Stellenbosch University, P.O. Box 19063, Tygerberg, Cape Town 7505, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Abayomi
authors.affiliation: Haematology Division, Department of Pathology, Faculty of Medicine and Health Science, Stellenbosch University, P.O. Box 19063, Tygerberg, Cape Town 7505, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: Ipp
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D019562:Viral Load; D055815:Young Adult
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D015415:Biomarkers; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides