An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells

Marthandan, Shiva and Hyland, Paul and Pawelec, Graham and Barnett, Yvonne A. (2013) An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells. Immunity & Ageing, 10. p. 7. ISSN 1742-4933

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Background: The research literature has documented age-related increases in genetic damage, including oxidative DNA damage, in human T lymphocytes, in vitro and ex vivo. Such damage has the potential to interfere with the ability of the T cells to proliferate at times when they need to, such as when antigen challenged. The consequence of this could be a sub-optimal immune response in vivo.Context and purpose: The purpose of the research reported in this paper was to investigate the impact of two antioxidants, which can be administered in vivo, Ebselen and N-acetyl L-cysteine, on the age-related increase in genetic damage, and on T cell proliferation and lifespan. In vitro human T cell clones, ex vivo peripheral blood mononuclear cells or T cells were supplemented with different concentrations of antioxidants, under standard conditions and for different periods of time. A range of assays were then applied in order to determine any impact of the antioxidants.Results: 30 μM ebselen or 7.5 mM N-acetyl L-cysteine supplementation resulted in a significantly higher intracellular GSH: GSSG ratio. This increased ratio was accompanied by reduced levels of oxidative DNA damage in established CD4+ human T cell clones, from a young or a middle-aged donor. Additionally, cultures of primary human peripheral blood mononuclear cells and CD4+ T cells from donors aged 25-30 or 55-60 years were also supplemented with these agents. Cells from all sources exhibited increased proliferation, and in the case of the T cell clones, an increase in cumulative population doublings. Neither ebselen nor N-acetyl L-cysteine had such effects on clones supplemented from the midpoint of their in vitro lifespan.Conclusions: Ebselen and N-acetyl L-cysteine, under certain conditions, may have anti-immunosenescent potential in T cells in in vitro clonal and ex vivo polyclonal culture models.

Item Type: Journal Article
Keywords: Ebselen, NAC, PBMCs, Proliferative capacity, Lifespan, DNA damage, GSH: GSSG ratio, Total glutathione, Oxidative DNA-damage, Repair capacity, In-vitro, Glutathione, Age, Apoptosis, Stress, Clones, Inhibition, Activation
Faculty: ARCHIVED Faculty of Science & Technology (until September 2018)
SWORD Depositor: Symplectic User
Depositing User: Symplectic User
Date Deposited: 20 Dec 2019 08:57
Last Modified: 09 Sep 2021 19:02

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