Old dogs and new tricks: defective peripheral regulatory T cell generation in aged mice.

Tolerance is a developmentally acquired property of the vertebrate immune system, in part ensured by regulatory CD4⁺ lymphocytes (Treg cells) expressing the Foxp3 transcription factor. Recent work has shown that thymic emigrants are the preferential source of peripherally generated Treg cells. A new report in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 2598-2604] describes a cell autonomous defect in Foxp3 induction in aged CD4⁺ cells in mice. Immune homeostasis becomes progressively less robust as ontogeny gives way to aging, and a key feature of senescence is thymic involution and the impaired T-cell turnover that follows. In this Commentary, we discuss the implications of these recent findings for our understanding of the induction of tolerance to peripheral antigens in aging.