SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures

Marthandan, Shiva and Freeburn, Robin and Steinbrecht, Susanne and Pawelec, Graham and Barnett, Yvonne A. (2014) SENIEUR status of the originating cell donor negates certain ‘anti-immunosenescence’ effects of ebselen and N-acetyl cysteine in human T cell clone cultures. Immunity & Ageing, 11. p. 17. ISSN 1742-4933

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Official URL: https://doi.org/10.1186/s12979-014-0017-5

Abstract

BACKGROUND: Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. METHODS: T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. RESULTS: In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. CONCLUSIONS: The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

Item Type: Journal Article
Keywords: DNA damage, ERK, Ebselen, GSH:GSSG ratio, Immunosenescence, JNK, Lifespan, MAP kinases, NAC, Proliferative capacity, SENIEUR, Total glutathione, p38
Faculty: ARCHIVED Faculty of Science & Technology (until September 2018)
Depositing User: Ian Walker
Date Deposited: 06 Dec 2019 12:49
Last Modified: 06 Feb 2020 16:21
URI: http://arro.anglia.ac.uk/id/eprint/705019

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