The aging T cell response: Increased T cell death leads to decreased memory progression in a mouse model

Alterations in the function and structure of the immune system are a hallmark of aging. Consistent with a deteriorating immunity is an age-associated increase in morbidity and mortality from infectious diseases, highlighting the need for improvement of immunizations targeted for the elderly and other interventions during illness. In this study, we have investigated several possible mechanisms for the deficiencies in the aging immune system using a murine model.;Chapter two examines the effects of reactive oxygen species on the T cells of young and aged mice. Unstimulated T cells from aged mice were more resistant to death induced by hydrogen peroxide than were the young. Using a synthetic antioxidant, we demonstrated that MnTBAP facilitated the apoptotic rescue of T cells from the aged mice better than their young counterparts.;In the third chapter, we explored the phenotypes of immune memory populations in splenic and lymph node tissues from the mice. T cells of aged mice have a skewed memory phenotype resulting in a decreased CM:EM ratio. The disproportional number of cells having an effector memory phenotype suggests that the cells are not progressing through successive divisions to become terminally differentiated central memory cells, which mediate protective immunity in the host. This means vaccination will be less effective and recurrent infection more likely in the elderly.;As increased numbers of individuals are living longer, treatments aimed at improving immune dysfunction in the elderly must be given priority. The experiments presented here give us additional insight into the complexities of the aging T cell immune response. With a better knowledge of these mechanisms, optimal treatments and vaccine strategies can be designed to benefit the elderly.;In chapter one, we investigate death susceptibility of activated T cells and how it impacts cell progression to successive generations in young and aged mice. CD4+ and CD8+ T cells from aged mice demonstrate increased apoptosis upon activation, which is only partly alleviated by IL-2. Aged mice also have increased numbers of unresponsive CD4+ T cells, which proliferate with overall slower kinetics when compared to their young counterparts.