Project supported by the VERUM Foundation
Adaptive immune responses require the extensive clonal proliferation of small initial numbers of antigen-specific T cells; the extent to which this capacity is compromized in the elderly or in patients may relate to the individual´s degree of success in mounting protective immune responses. A systematic study of potential differences in the ability of T cells from different donors to undergo clonal expansion in vitro has never been attempted. For this purpose, it is necessary to generate T cell clones and culture each single clone to the end of its finite lifespan. Only then can one assess average longevities, and not merely maximum longevity of the longest-lived clone in the population. Therefore, in this project, we propose to compare the average and maximal longevity of T cells from young healthy donors with those from very old extremely healthy (SENIEUR) donors and others. We will establish the degree of variation of clonal expansion ability (CEA) in groups of donors: 1) young healthy, 2) very old SENIEUR, 3) very old donors participating in longitudinal ageing studies, 4) very old donors participating in vaccination studies, 5) clinically-depressed old patients, 6) Werner´s syndrome patients, 7) dietary supplementation subjects, 8) chronically virally-infected patients. These data will tell us whether an individual´s CEA is relevant to his health status, and in the case of the longitudinal study, directly indicate whether decreases in CEA predict more rapid demise. At least some of the derived T cell clones will also be preserved for further study on their functional and genomic integrity, by ourselves and by other groups.