Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity.
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 maintai...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1826289240959352832 |
|---|---|
| author | Komatsu, N Mariotti-Ferrandiz, M Wang, Y Malissen, B Waldmann, H Hori, S |
| author_facet | Komatsu, N Mariotti-Ferrandiz, M Wang, Y Malissen, B Waldmann, H Hori, S |
| author_sort | Komatsu, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:25:53Z |
| format | Journal article |
| id | oxford-uuid:a595ef49-f87e-47e6-9ec3-d010a3ce9e1a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:25:53Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:a595ef49-f87e-47e6-9ec3-d010a3ce9e1a2022-03-27T02:41:30ZHeterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a595ef49-f87e-47e6-9ec3-d010a3ce9e1aEnglishSymplectic Elements at Oxford2009Komatsu, NMariotti-Ferrandiz, MWang, YMalissen, BWaldmann, HHori, SNatural 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. |
| spellingShingle | Komatsu, N Mariotti-Ferrandiz, M Wang, Y Malissen, B Waldmann, H Hori, S Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title | Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title_full | Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title_fullStr | Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title_full_unstemmed | Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title_short | Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. |
| title_sort | heterogeneity of natural foxp3 t cells a committed regulatory t cell lineage and an uncommitted minor population retaining plasticity |
| work_keys_str_mv | AT komatsun heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity AT mariottiferrandizm heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity AT wangy heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity AT malissenb heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity AT waldmannh heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity AT horis heterogeneityofnaturalfoxp3tcellsacommittedregulatorytcelllineageandanuncommittedminorpopulationretainingplasticity |