. With age, the proportion of memory T cells increases, while the proportion and number of naive T cell decreases. Memory T cells are more sensitive to antigenic stimulation and less dependent on co-stimulation signals, as compared to naïve T cells. Differentiation of naïve T cells into memory T cells is accompanied by an increase in T cell reactivity to self-peptide/MHC complexes, which allowed for positive selection of their naïve precursors in the thymus.. We envisage that in geriatric age memory Th1-type autoreactivity leads to age-associated immune hyporeactivity, atherosclerosis and degenerative neuropathology, such as Alzheimer’s and Parkinson’s diseases, whereas autoreactive memory Th2 cells could promote tumorigenesis.. Stimulation of adaptive immunoregulatory mechanisms by polyclonal T-cell vaccination could constrain the development of age-related T-cell autoreactivity surplus. Another approach to immune system “rejuvenation” could involve adoptive cell transfer of naïve T cells with a view to restrain the expansion of pathological memory T cells and support immune responsiveness to novel antigenic challenges. The proposed concept conjectures the occurrence of a hard-wired immunological clock that could determine the duration of life, which theoretically could be subject to immune-based therapy.

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