The frequency of regulatory CD3+CD8+CD28-CD25+ T lymphocytes in human peripheral blood increases with age.

Aging is commonly associated with immune deficiency and dysregulation. The aging of the immune system involves a progressive reduction in naı¨ve T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. We have investigated frequency, phenotype, and function of CD3CD8CD28– CD25 T cells in healthy volunteers over a wide age range. We demonstrate that the frequency of CD3CD8CD28–CD25 T cells in healthy volunteers increases with age. Peripheral CD3CD8 CD28–CD25 T cells share phenotypic and functional features with CD3CD4CD25 regulatory T cells (Tregs): In particular, they strongly express CTLA-4 and forkhead box P3. We observed that in vitro, functional titration assays of CD3CD8 CD28–CD25 T cells show equivalent regulatory function in young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. Finally, CD3CD8CD28–CD25 T cells seem to specifically express the CD122 receptor. Altogether, these observations demonstrate an increase in peripheral blood CD8 Tregs associated with aging. J. Leukoc. Biol. 84: 000–000; 2008.