The Scientific objectives are to obtain insights into the basic cellular and molecular mechanisms underlying the decreased proliferative and functional capacity of aged T lymphocytes and to identify those characteristics which are critical for ageing processes. The ultimate aim is to use this knowledge to examine ways of delaying or preventing T cell senescence in these preclinical in vitro model systems and to examine the effects of these manipulations on the expression of the identified characteristics paralleling T cell ageing.

The expected achievements of this project are

1. successful scale-up for the generation of sufficient T cell clones (TCC) for distribution to members and transfer of T cell culture and cloning technology;
2. the establishment of candidate causative factors for T cell immunosenescence in longitudinal in vitro models of ageing and their validation in multiple laboratories in a quality-control exercise in vitro; finally, selection of those for testing in vivo;
3. the validation of these selected candidates on T cells ex vivo from a large range of donors of different ages and in different states of physical and mental health in cross-sectional and longitudinal studies;
4. the manipulation of T cell senescence in vitro in the ageing model and assessment of the impact of such manipulations on function and surface phenotypes of the cells for monitoring purposes;
5. carrying out trials involving proband manipulation, such as dietary supplementation and eventually other senescence-modulating interventions in vivo, and monitoring their T cells for age-associated changes.

The coordination objectives are

1. to re-establish a central facility (CF) to collect, produce and bank cells and data pertaining to these, for use by members of ImAginE. This requires re-establishing and modernizing the web-site (still extant under www.medizin.uni-tuebingen/eucambis/) as well as the physical and virtual cell and data banks;
2. to generate sufficient in vitro cultured T cell clones for distribution to selected members for study in the first phase of the project. These must be expanded to large numbers and cryopreserved [using the EUCAMBIS equipment]. Each batch must be pre-checked for viability and sterility before shipping on dry ice to members;
3. to collect and integrate data from members obtained using these centrally-distributed materials for comparison and quality control at the CF;
4. to facilitate communication between relevant groups by establishing an interactive web site for display of the latest central data analyses from the ImAginE studies;
5. to agree on the characteristics to be studied in the second phase of the project, ie. screening on the unique donor material available to the various members;
6. to collect and integrate these data at the central facility;
7. to coordinate attempts to develop methods for extending the lifespan of T cells in vitro;
8. to assess whether such interventions may be possible in vivo;
9. to organise meetings and short-term personnel exchange to facilitate the performance of the project.