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Eur J Immunol. 2013 Oct;43(10):2598-604. doi: 10.1002/eji.201343532. Epub 2013 Jul 31.

Extrathymic induction of Foxp3⁺ regulatory T cells declines with age in a T-cell intrinsic manner.

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Institut National de la Santé et de la Recherche Médicale U1013, Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, Paris, France.


Extrathymically induced Foxp3⁺ regulatory T (Treg) cells contribute to the pool of Treg cells and are implicated in the maintenance of immune tolerance at environmental interfaces. The impact of T-cell senescence on their generation and function is, however, poorly characterized. We report here that steady-state induction of Foxp3 is impaired in aged T cells in vivo. In vitro assays further revealed that this defective generation of Treg cells was independent from the strength of TCR stimulation and arose before T-cell proliferation. Importantly, they also revealed that this impairment of Foxp3 induction is unrelated to known age-related T-cell defects, such as IL-2 secretion impairment, accumulation of activated T-cell populations, or narrowing of the T-cell repertoire. Finally, a loss of extrathymic induction of Foxp3 and tolerance to minor-mismatched skin graft were observed in aged mice treated by nondepleting anti-CD4 antibody. The T-cell intrinsic impairment of Treg-cell generation revealed here highlights age as a key factor to be considered in immune tolerance induction.


Aging; Foxp3; Regulatory T (Treg) cells; Transplantation

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