Heterogeneity of natural Foxp3+ T cells: A committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity
Heterogeneity of natural Foxp3+ T cells: A committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity
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DOI：
10.1073/pnas.0811556106
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发表时间：
2009-02-10
影响因子：
11.1
通讯作者：
Hori, Shohei
中科院分区：
文献类型：
--
作者：
Komatsu, Noriko;Mariotti-Ferrandiz, Maria Encarnita;Hori, Shohei
天然调节性T细胞（T-reg）代表了致力于抑制功能的T淋巴细胞的独特谱系，并且转录因子Foxp 3的表达被认为特异性地鉴定该谱系。在此，我们报道，尽管大多数天然的CD 4（+）Foxp 3（+）T细胞在过继转移给淋巴细胞减少或淋巴细胞缺乏的受体后保持稳定的Foxp 3表达，但在CD 25（-）亚群中富集的一小部分实际上失去了Foxp 3表达。这些Foxp 3（+）T细胞中的一些采用效应辅助T细胞（T-h）功能，而一些保留了先前Foxp 3表达的“记忆”，激活后重新获得Foxp 3。这种少数“不稳定”群体对细胞因子信号表现出灵活的反应，依赖于转化生长因子-β来维持Foxp 3表达，并通过在体外分化成效应T-h来对其他细胞因子作出反应。相比之下，CD 4（+）Foxp 3（+）CD 25（高）T细胞即使在多轮细胞分裂后也对这种向效应Th的转化具有抵抗力。这些结果表明，天然Foxp 3（+）T细胞是由定型Treg谱系和具有发育可塑性的未定型亚群组成的异质群体。免疫学
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 Th even after many rounds of cell division. These results demonstrate that natural Foxp3(+) T cells are a heterogeneous population consisting of a committed Treg lineage and an uncommitted subpopulation with developmental plasticity. IMMUNOLOGY