Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1073/pnas.0811556106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

10/02/2009

Volume

106

Pages

1903 - 1908

Keywords

Adoptive Transfer, Animals, Cell Differentiation, Cell Lineage, Cytokines, Forkhead Transcription Factors, Lymphocyte Subsets, Mice, Mice, Inbred C57BL, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Transforming Growth Factor beta