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Open Access Research

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

Shiva Marthandan1, Paul Hyland2, Graham Pawelec3 and Yvonne Barnett4*

Author Affiliations

1 Leibniz Institute for Age Research, Jen Age (Jena Centre for Systems Biology of Ageing), Beutenbergstrasse 11, Jena, D-07745, Germany

2 National Blood Authority, Canberra, ACT 2601, Australia

3 Tübingen Ageing and Tumour Immunology Group, Center for Medical Research, University of Tübingen Clinical School, Waldhörnlestr. 22, Tübingen, D-72072, Germany

4 School of Science and Technology, College of Arts and Science, Nottingham Trent University, Clifton Lane, Nottingham, England, NG11 8NS, UK

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Immunity & Ageing 2013, 10:7  doi:10.1186/1742-4933-10-7

Published: 21 February 2013

Abstract

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.

Keywords:
Ebselen; NAC; PBMCs; Proliferative capacity; Lifespan; DNA damage; GSH: GSSG ratio; Total glutathione