Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Department of Neurology, Collegium Medicum, University of Zielona Gora, Zielona Gora, Poland.
J Neuroinflammation. 2023 Nov 23;20(1):275. doi: 10.1186/s12974-023-02957-w.
Regulatory T cells (Tregs) are involved in the systemic immune response after ischemic stroke. However, their role remains unclear, and the effect appears to be both neuroprotective and detrimental. Treg suppressor function may result in immunodepression and promote stroke-associated infection (SAI). Thus we assume that the bidirectional effects of Tregs may be in part attributed to the intracellular transcription factor Helios. Tregs with Helios expression (H+ Tregs) constitute 70-90% of all Treg cells and more frequently than Helios-negative Tregs (H- Tregs) express molecules recognized as markers of Tregs with suppressor abilities.
We prospectively assessed the circulating Treg population with flow cytometry in 52 subjects on days 1, 3, 10 and 90 after ischemic stroke and we compared the results with those obtained in concurrent age-, sex- and vascular risk factor-matched controls. At all studied time points the percentage of H+ Tregs decreased in stroke subjects-D1: 69.1% p < 0.0001; D3: 62.5% (49.6-76.6), p < 0.0001; D10: 60.9% (56.5-72.9), p < 0.0001; D90: 79.2% (50.2-91.7), p = 0.014 vs. controls: 92.7% (81.9-97.0) and the percentage of H- Tregs increased accordingly. In patients with SAI the percentage of pro-suppressor H+ Tregs on post-stroke day 3 was higher than in those without infection (p = 0.03). After adjustment for confounders, the percentage of H+ Tregs on day 3 independently correlated with SAI [OR 1.29; CI 95%: 1.08-1.27); p = 0.02]. Although the percentage of H+ Tregs on day 3 correlated positively with NIHSS score on day 90 (rS = 0.62; p < 0.01) and the infarct volume at day 90 (rS = 0.58; p < 0.05), in regression analysis it was not an independent risk factor.
On the first day after stroke the proportion of H+ vs. H- Tregs changes in favor of pro-inflammatory H- Tregs, and this shift continues toward normalization when assessed on day 90. A higher percentage of pro-suppressive H+ Tregs on day 3 independently correlates with SAI and is associated positively with NIHSS score, but it does not independently affect the outcome and stroke area in the convalescent phase of stroke.
调节性 T 细胞（Tregs）参与缺血性中风后的全身免疫反应。然而，它们的作用仍不清楚，其影响似乎既有神经保护作用，也有不利作用。Treg 的抑制功能可能导致免疫抑制，并促进与中风相关的感染（SAI）。因此，我们假设 Tregs 的双向作用部分归因于细胞内转录因子 Helios。表达 Helios 的 Treg 细胞（H+ Tregs）构成所有 Treg 细胞的 70-90%，并且比 Helios 阴性 Treg 细胞（H- Tregs）更频繁地表达被认为具有抑制能力的 Treg 标志物的分子。
我们前瞻性地使用流式细胞术在缺血性中风后第 1、3、10 和 90 天评估了 52 名受试者的循环 Treg 群体，并将结果与同期年龄、性别和血管危险因素匹配的对照组进行比较。在所有研究时间点，中风患者的 H+ Treg 百分比均下降-D1：69.1%，p < 0.0001；D3：62.5%（49.6-76.6），p < 0.0001；D10：60.9%（56.5-72.9），p < 0.0001；D90：79.2%（50.2-91.7），p = 0.014 与对照组相比：92.7%（81.9-97.0），相应地，H- Treg 的百分比增加。在发生 SAI 的患者中，中风后第 3 天的前抑制性 H+ Treg 百分比高于未感染的患者（p = 0.03）。在调整混杂因素后，第 3 天的 H+ Treg 百分比独立与 SAI 相关[OR 1.29；95%CI：1.08-1.27）；p = 0.02]。尽管第 3 天的 H+ Treg 百分比与第 90 天的 NIHSS 评分呈正相关（rS = 0.62；p < 0.01），与第 90 天的梗死体积呈正相关（rS = 0.58；p < 0.05），但在回归分析中，它不是独立的危险因素。
中风后第一天，H+与 H- Treg 的比例向促炎的 H- Treg 倾斜，并且当在第 90 天评估时，这种转变继续向正常化方向发展。第 3 天较高比例的前抑制性 H+ Treg 与 SAI 独立相关，与 NIHSS 评分呈正相关，但在中风恢复期不会独立影响预后和中风面积。
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