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Originally published online as doi:10.1189/jlb.0907627 on September 9, 2008

Published online before print September 9, 2008
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(Journal of Leukocyte Biology. 2008;84:1454-1461.)
© 2008 by Society for Leukocyte Biology

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

Rita Simone*,1, Anna Zicca{dagger},2 and Daniele Saverino*,3

* Department of Experimental Medicine, Section of Human Anatomy, University of Genova, Genova, Italy; and
{dagger} Department of Biomorphology and Biotechnologies, University of Messina, Messina, Italy

3 Correspondence: University of Genova, Department of Experimental Medicine, Section of Human Anatomy, Via De Toni, 14, 16132 Genova, Italy. E-mail: daniele.saverino{at}unige.it

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.

Key Words: aging • Treg • CD4+CD25+