DFG Project Pa 361/7-1

It is hypothesised that dysregulated immune function in the T cell compartment contributes to numerous diseases of ageing in humans. A unifying theme in this context is chronic antigenic stimulation of T cells by pathogens (eg. viral and bacterial antigens), autoantigens (and cancer antigens). This project will seek to elucidate T cell dysfunction in a model of ageing under chronic antigenic stimulation in vitro and ex vivo and to manipulate the T cells to circumvent these changes in a safe manner. Biomarkers of ageing contributing to the definition of an immunological risk profile will be monitored in cross-sectional and longitudinal studies in the elderly and in supplementation studies. The aim is to predict susceptibility to morbidity and mortality in the elderly based on immunological parameters and to learn to manipulate these for clinical benefit. The objectives of the present proposal are to elucidate the changes occurring in longitudinal models of chronically antigen-exposed ageing human T cells in order to identify "biomarkers" of immunosenescence and to define Immunological Risk Profiles, IRP, for lymphocyte dysfunction which contribute to age-associated disease. The occurrence of these changes in vivo in the healthy and diseased elderly will be ascertained in cross-sectional and longitudinal studies. In vitro manipulation of T cells to prevent such phenotypic and functional alterations associated with compromised immune function will be sought.