Oxidative inactivation of CD45 protein tyrosine phosphatase may contribute to T lymphocyte dysfunction in the elderly

The decline in T lymphocyte function during ageing has been linked to changes in intracellular signalling pathways. Oxidative damage has long been thought to be involved in the ageing process and we investigated a link between ageing, oxidation and T cell signalling focusing on the membrane phosphatase CD45. We investigated the relative sensitivity of CD45 to oxidative inactivation and then compared the phosphatase activity of CD45 in blood lymphocytes from elderly and young volunteers and related this to intracellular levels of the antioxidant glutathione. The CD45 phosphatase was particularly sensitive to oxidative inactivation compared to total Jurkat T cell PTP activity. The IC50 with H(2)O(2) was 3 mM for CD45 at which concentration there was a minimal decrease in global PTP activity. In normal peripheral blood CD4(+) T cells the IC50 was much lower at 54 microM. In a group of elderly healthy individuals, whose T cell responses to mitogen were depressed, PB lymphocyte CD45 phosphatase activity was decreased by about 60% compared to young controls. There was no difference in intracellular levels of glutathione. The loss of CD45 activity in lymphocytes from the elderly may underlie poor T cell function associated with ageing. The relative sensitivity of CD45 to oxidative damage may result from its location in the plasma membrane, where it might be more accessible to extracellular oxidants.