Extrathymic induction of Foxp3⁺ regulatory T cells declines with age in a T-cell intrinsic manner. - Institut Pasteur Access content directly
Journal Articles European Journal of Immunology Year : 2013

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.

Domains

Immunology

Dates and versions

pasteur-00912507 , version 1 (02-12-2013)

Identifiers

Cite

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, 2013, 43 (10), pp.2598-604. ⟨10.1002/eji.201343532⟩. ⟨pasteur-00912507⟩
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