Department of Translational Medicine, Neurology Unit, Movement Disorders Centre, University of Piemonte Orientale, Corso Mazzini 18, 28100, Novara, Italy.
PhD Program in Medical Sciences and Biotechnology, University of Piemonte Orientale, 28100, Novara, Italy.
J Neurol. 2023 May;270(5):2776-2783. doi: 10.1007/s00415-023-11635-z. Epub 2023 Feb 25.
Dysregulation of the CD4 + T cell compartment occurs in Parkinson's Disease (PD). Nonetheless, the exact relationship with dopamine transporter (DAT) SPECT denervation patterns is currently unknown.
Expression of transcription factors and levels of circulating CD4 + T cell subsets were assessed in peripheral blood mononuclear cells (PBMC) from 23 newly diagnosed drug-naïve PD patients. Semi-quantitative [I]-FP-CIT SPECT data, i.e. uptake in the most and least affected putamen (maP, laP) and caudate (maC, laC), total striatal binding ratio (tSBR), and total putamen-to-caudate ratio (tP/C) were obtained.
FOXP3 mRNA levels correlated with the uptake in maC (r = - 0.542, P = 0.011), laP (r = - 0.467, P = 0.033), and tSBR (r = - 0.483, P = 0.027). Concerning flow cytometry analysis of circulating CD4 + T cell subsets, a significant relationship between tP/C, caudate uptake, and the levels of both T helper (Th)1 and 2, was detected. Furthermore, we found significant correlations between the uptake in maP and the total count of naïve and activated T regulatory cells (Treg) (r = - 0.717, P = 0.001; r = - 0.691, P = 0.002), which were confirmed after the Benjamini-Hochberg correction for multiple comparisons using a false discovery rate at level q = 0.10. Levels of circulating naïve Treg were higher (P = 0.014) in patients with more extensive dopaminergic denervation, suggesting a compensatory phenomenon.
Peripheral CD4 + T cell immunity is involved in early-stage PD and novel correlations with striatal DAT loss were observed.
CD4+T 细胞的失调发生在帕金森病（PD）中。尽管如此，与多巴胺转运蛋白（DAT）SPECT 去神经支配模式的确切关系目前尚不清楚。
评估了 23 例新诊断的未经药物治疗的 PD 患者外周血单个核细胞（PBMC）中转录因子的表达和循环 CD4+T 细胞亚群的水平。获得了半定量[I]-FP-CIT SPECT 数据，即最大和最小受影响的壳核（maP，laP）和尾状核（maC，laC）的摄取、总纹状体结合比（tSBR）和总壳核-尾状核比（tP/C）。
FOXP3 mRNA 水平与 maC（r=-0.542，P=0.011）、laP（r=-0.467，P=0.033）和 tSBR（r=-0.483，P=0.027）的摄取相关。关于循环 CD4+T 细胞亚群的流式细胞术分析，发现 tP/C、尾状核摄取与 Th1 和 Th2 水平之间存在显著关系。此外，我们发现 maP 摄取与幼稚和激活 T 调节细胞（Treg）的总计数之间存在显著相关性（r=-0.717，P=0.001；r=-0.691，P=0.002），这在用错误发现率 q=0.10 进行多次比较的 Benjamini-Hochberg 校正后得到了证实。循环幼稚 Treg 水平在多巴胺能神经支配程度较高的患者中较高（P=0.014），表明存在代偿现象。
外周 CD4+T 细胞免疫参与了早期 PD，并且观察到与纹状体 DAT 丢失的新相关性。
