Multiparameter single-cell profiling of human CD4+FOXP3+ regulatory T-cell populations in homeostatic conditions and during graft-versus-host disease
Multiparameter single-cell profiling of human CD4+FOXP3+ regulatory T-cell populations in homeostatic conditions and during graft-versus-host disease
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DOI：
10.1182/blood-2013-02-482539
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发表时间：
2013-09-05
期刊：
影响因子：
20.3
通讯作者：
Rogge, Lars
中科院分区：
文献类型：
--
作者：
Dong, Shen;Maiella, Sylvie;Rogge, Lars
了解人类CD 4（+）FOXP 3（+）调节性T细胞（Tcells）的异质性及其谱系重编程的潜力对于将Treg治疗推向临床至关重要。使用多参数单细胞分析技术，我们探讨了人类TCR 4在健康供体和异基因造血干细胞移植（alloHSCT）后的异质性和功能多样性。人类T细胞在转录因子、归巢受体和炎性细胞因子的表达方面显示出与传统CD 4（+）效应T细胞相似的复杂性水平。产生白细胞介素-17A或干扰素-γ的罕见Treg的单细胞分析显示，Th 17或Th 1细胞和TcB的基因表达特征重叠。为了评估Treg稳态是否受到炎症和淋巴细胞减少环境的影响，我们描述了alloHSCT后早期患者的Treg区室。该分析表明，与耐受患者相比，发生急性移植物抗宿主病的患者中Treg明显耗竭，具有幼稚表型。然而，单细胞分析显示，CD 4（+）FOXP 3（+）T细胞保持Treg基因表达特征，Treg抑制活性得以保留。我们的研究证实，单细胞水平的异质性，而不是CD 4（+）FOXP 3（+）T细胞的谱系重编程，解释了人类TcB的显着复杂性和功能多样性。
Understanding the heterogeneity of human CD4(+)FOXP3(+) regulatory T cells (Tregs) and their potential for lineage reprogramming is of critical importance for moving Treg therapy into the clinics. Using multiparameter single-cell analysis techniques, we explored the heterogeneity and functional diversity of human Tregs in healthy donors and in patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). Human Tregs displayed a level of complexity similar to conventional CD4(+) effector T cells with respect to the expression of transcription factors, homing receptors and inflammatory cytokines. Single-cell profiling of the rare Treg producing interleukin-17A or interferon-gamma showed an overlap of gene expression signatures of Th17 or Th1 cells and of Tregs. To assess whether Treg homeostasis is affected by an inflammatory and lymphopenic environment, we characterized the Treg compartment in patients early after alloHSCT. This analysis suggested a marked depletion of Treg with a naive phenotype in patients developing acute graft-versus-host disease, compared with tolerant patients. However, single-cell profiling showed that CD4(+) FOXP3(+) T cells maintain the Treg gene expression signature and Treg-suppressive activity was preserved. Our study establishes that heterogeneity at the single-cell level, rather than lineage reprogramming of CD4(+)FOXP3(+) T cells, explains the remarkable complexity and functional diversity of human Tregs.