Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2009

Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity.

Abstract

Natural regulatory T cells (T(reg)) represent a distinct lineage of T lymphocytes committed to suppressive functions, and expression of the transcription factor Foxp3 is thought to identify this lineage specifically. Here we report that, whereas the majority of natural CD4(+)Foxp3(+) T cells maintain stable Foxp3 expression after adoptive transfer to lymphopenic or lymphoreplete recipients, a minor fraction enriched within the CD25(-) subset actually lose it. Some of those Foxp3(-) T cells adopt effector helper T cell (T(h)) functions, whereas some retain "memory" of previous Foxp3 expression, reacquiring Foxp3 upon activation. This minority "unstable" population exhibits flexible responses to cytokine signals, relying on transforming growth factor-beta to maintain Foxp3 expression and responding to other cytokines by differentiating into effector T(h) in vitro. In contrast, CD4(+)Foxp3(+)CD25(high) T cells are resistant to such conversion to effector T(h) even after many rounds of cell division. These results demonstrate that natural Foxp3(+) T cells are a heterogeneous population consisting of a committed T(reg) lineage and an uncommitted subpopulation with developmental plasticity.

Dates and versions

hal-00407810 , version 1 (27-07-2009)

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Noriko Komatsu, Maria Encarnita Mariotti-Ferrandiz, Ying Wang, Bernard Malissen, Herman Waldmann, et al.. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity.. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (6), pp.1903-8. ⟨10.1073/pnas.0811556106⟩. ⟨hal-00407810⟩

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