Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis.

Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis.
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DOI:
10.1371/journal.pone.0037393
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Salomao R
Salomao R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brunialti MK;Santos MC;Rigato O;Machado FR;Silva E;Salomao R

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据报道,脓毒症患者(SP)从Th 1向Th 2转变,以及Treg CD 4 +T细胞亚群增加。此外,这些患者表现出单核细胞功能的调节,在LPS刺激后促炎细胞因子的产生减少,这类似于交替活化的巨噬细胞的表型。在这项研究中,我们评估了T细胞分化为Th 1,Th 17和Treg亚群的百分比,以及单核细胞表达交替激活的单核细胞/巨噬细胞(AAM)的标志物的百分比在SP。外周血单核细胞(PBMC)从32名健康志愿者(HV)和SP在入院时(D 0,n = 67)和治疗7天后(D 7,n = 33)。    Th 1和Th 17(CD 3 + CD 8 −)淋巴细胞通过IFN-γ和IL-17的细胞内检测分别自发和PMA/Io刺激后鉴定,Treg细胞通过Foxp 3 + CD 127-表达鉴定。评价单核细胞的CD 206和CD 163表达。通过流式细胞术测量全血样品中的CD 4 +T淋巴细胞的绝对数。适当时应用Mann-Whitney或Wilcoxon检验。PMA/Io刺激后,SP组Th 1细胞百分比低于HV组,而Th 17细胞百分比高于HV组。在患者的随访样本中,与D 0样本相比,在D 7观察到更高百分比的Th 1细胞和更低百分比的Th 17细胞。Treg细胞保持不变。脓毒症患者显示表达CD 163和CD 206的单核细胞比例显著增加。在体外刺激下,在入院时SP中产生IL-17的T辅助淋巴细胞的百分比高于HV,而产生IFN-γ的百分比较低,这种模式在随访期间逆转。CD 163和CD 206的表达增加表明单核细胞在脓毒症期间可获得AAM表型。
A shift from Th1 to Th2 as well as an increase in Treg CD4+T cell subsets has been reported in septic patients (SP). Furthermore, these patients display modulation of monocyte function, with reduced production of pro-inflammatory cytokines upon LPS stimulus, which resembles the phenotype of alternatively activated macrophages. In this study, we evaluated the percentages of T cells differentiated into Th1, Th17 and Treg subsets, as well as the percentage of monocytes expressing markers of alternatively activated monocytes/macrophages (AAM) in SP. Peripheral blood mononuclear cells (PBMC) were obtained from 32 healthy volunteers (HV) and from SP at admission (D0, n = 67) and after 7 days of therapy (D7, n = 33). Th1 and Th17 (CD3+CD8−) lymphocytes were identified by the intracellular detection of IFN-γ and IL-17, respectively, spontaneously and after PMA/Io stimulation, and Treg cells were identified by Foxp3+CD127- expression. Monocytes were evaluated for CD206 and CD163 expression. Absolute numbers of CD4+T lymphocytes were measured in whole blood samples by flow cytometry. The Mann-Whitney or Wilcoxon test was applied, as appropriate. The percentage of Th1 cells was lower in SP than in HV at admission after PMA/Io stimulation, whereas the percentage of Th17 cells was higher. In patients’ follow-up samples, a higher percentage of Th1 cells and a lower percentage of Th17 cells were observed on D7 compared with the D0 samples. Treg cells remained unchanged. Septic patients showed a markedly increased proportion of monocytes expressing CD163 and CD206. Upon in vitro stimulus, the percentage of T helper lymphocytes producing IL-17 was higher in SP than in HV at admission, and the percentage producing IFN-γ was lower, a pattern that was reversed during follow-up. The increased expression of CD163 and CD206 indicates that monocytes may acquire the AAM phenotype during sepsis.
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期刊: FASEB JOURNAL
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