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 naïve T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. We have investigated frequency, phenotype, and function of CD3 + CD8 + CD28 − CD25 + T cells in healthy volunteers over a wide age range. We demonstrate that the frequency of CD3 + CD8 + CD28 − CD25 + T cells in healthy volunteers increases with age. Peripheral CD3 + CD8 + CD28 − CD25 + T cells share phenotypic and functional features with CD3 + CD4 + CD25 + regulatory T cells (Tregs): In particular, they strongly express CTLA‐4 and forkhead box P3. We observed that in vitro, functional titration assays of CD3 + CD8 + 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, CD3 + CD8 + CD28 − CD25 + T cells seem to specifically express the CD122 receptor. Altogether, these observations demonstrate an increase in peripheral blood CD8 + Tregs associated with aging.