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Functional characterization of CD4 + T cells in aplastic anemia

机译:再生障碍性贫血中CD4 + T细胞的功能表征

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摘要

The role of CD4 + T cells in the pathogenesis of aplastic anemia (AA) is not well characterized. We investigate CD4 + T-cell subsets in AA. Sixty-three patients with acquired AA were studied. Th1 and Th2 cells were significantly higher in AA patients than in healthy donors (HDs; P = .03 and P = .006). Tregs were significantly lower in patients with severe AA than in HDs (P .001) and patients with nonsevere AA (P = .01). Th17 cells were increased in severeAA(P = .02) but normal in non-severe AA. Activated and resting Tregs were reduced in AA (P = .004; P = .01), whereas cytokine-secreting non-Tregs were increased (P = .003). Tregs from AA patients were unable to suppress normal effector T cells. In contrast, AA effector T cells were suppressible by Tregs from HDs. Th1 clonality in AA, investigated by high-throughput sequencing, was greater than in HDs (P = .03). Our results confirm that Th1 and Th2 cells are expanded and Tregs are functionally abnormal in AA. The clonally restricted expansion of Th1 cells is most likely to be antigen-driven, and induces an inflammatory environment, that exacerbate the functional impairment of Tregs, which are reduced in number.
机译:CD4 + T细胞在再生障碍性贫血(AA)发病机理中的作用尚不十分清楚。我们调查AA中的CD4 + T细胞亚群。研究了63例获得性AA的患者。 AA患者的Th1和Th2细胞显着高于健康供体(HD; P = .03和P = .006)。重度AA患者的Treg显着低于HDs(P <.001)和非严重AA患者(P = .01)。在严重AA中,Th17细胞增加(P = .02),在非严重AA中,Th17细胞增加。活化和静息的Tregs在AA中减少(P = .004; P = .01),而分泌细胞因子的非Tregs增加(P = .003)。来自AA患者的Treg不能抑制正常的效应T细胞。相反,AA效应T细胞可被来自HD的Tregs抑制。通过高通量测序研究,AA中的Th1克隆性比HD中的Th1克隆性更高(P = .03)。我们的结果证实,AA中Th1和Th2细胞扩增且Tregs功能异常。 Th1细胞的克隆限制扩增最可能是抗原驱动的,并诱导炎性环境,加剧了Tregs的功能损伤,Tregs的数量减少了。

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