Antioxidents or reduced oxygen tension as a defense system in T cells ex vivo and in vitro

Doctoral thesis English OPEN
Marthandan, SS (2009)

Age-related deterioration and dysregulation of T cell function, termed ‘immunosenescence’, may lead to increased mortality and morbidity in humans through greater susceptibility to infections and disease. Previous research from the group of Barnett, suggested that oxidative stress may play a role in the immunosenescence process, through resultant genomic instability, cell cycle delay and arrest. The aim of this research programme was to investigate the effect of the antioxidants, ebselen, NAcetyl L- Cysteine (NAC) or mitoQ or reduced oxygen (O2) tension on markers of T cell function and integrity using CD4+ T cell clones and ex vivo polyclonal human peripheral blood derived mononuclear cells or CD4+ T cells derived from healthy young and older aged donors. The results of this investigation revealed that 30μM ebselen or 7.5mM NAC supplementation significantly increased the lifespan and reduced levels of oxidative DNA damage in clones supplemented from a young in vitro age and in human peripheral blood mononuclear cells and CD4+ T cells ex vivo derived from either age group. The GSH:GSSG ratio was also significantly higher in supplemented clones and cells ex vivo. Ebselen or NAC were not able to bring about such biological effects in clones when supplemented from the midpoint of their in vitro lifespan. In this latter situation, age related changes in T cell physiology example: reduced DNA repair capacity, heat shock response and an accumulation of biomolecule damage may have contributed to these findings.
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    GROWTH RECORDS OF HUMAN CD4+ T CELL CLONES ......................................................... 215

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