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

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00912507
Contributor : Marie-Christine Vougny <>
Submitted on : Monday, December 2, 2013 - 11:26:24 AM
Last modification on : Tuesday, July 21, 2020 - 3:58:47 AM

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Maxime Carpentier, Pascal Chappert, Chantal Kuhn, Mélanie Lalfer, Héloïse Flament, et al.. Extrathymic induction of Foxp3⁺ regulatory T cells declines with age in a T-cell intrinsic manner.. European Journal of Immunology, Wiley-VCH Verlag, 2013, 43 (10), pp.2598-604. ⟨10.1002/eji.201343532⟩. ⟨pasteur-00912507⟩

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