National Pediatric Myoclonus Center, Orlando, FL, USA.
National Pediatric Neuroinflammation Organization, Inc., Orlando, FL, USA.
Clin Exp Immunol. 2018 Jul;193(1):103-112. doi: 10.1111/cei.13122. Epub 2018 Mar 24.
Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, due especially to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in paediatric neuroinflammation, we immunophenotyped cerebrospinal fluid (CSF) and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurological disorders (NIND), 312 with opsoclonus-myoclonus (OMS) and 23 with other inflammatory neurological disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency of 27% in infants and 3·3% in teens. Interindividual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation [human leucocyte antigen D-related (HLA-DR)], maturation (CD45RA, CD45RO) or intracellular cytokine staining [interleukin (IL)-4, interferon (IFN)-γ] failed to discriminate OMS and NIND groups. Of seven OMS immunotherapies/combinations, none altered the frequency of total CSF γδ T cells or subsets significantly. In OIND, the CSF γδ T cell frequency was < 10% for single samples of other paraneoplastic disorders [anti-neuronal nuclear antibody (ANNA)-1, PCA-1, teratoma-associated syndrome], cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis and encephalitis. This study provides new insights into CSF γδ T cells in the paediatric population. Although their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy and our age cut-off references for NIND are important findings for the design of future paediatric studies.
对儿童脑脊液（CSF）γδ T 细胞的研究受到限制，特别是由于缺乏对照数据。在成年人中，驻留在鞘内空间的γ/δ T 细胞（TCR-γδ）有时参与神经炎症。为了评估 γδ T 细胞在儿科神经炎症中的可能作用，我们使用流式细胞术对 100 名非炎症性神经疾病（NIND）患儿、312 名眼震-肌阵挛（OMS）患儿和 23 名其他炎症性神经疾病（OIND）患儿的脑脊液（CSF）和血液淋巴细胞进行免疫表型分析。在 NIND 中，CSF γδ T 细胞频率与患者年龄之间的负相关非常明显：婴儿的中位频率为 27%，青少年为 3.3%。年龄最小的个体之间的个体间差异最大。无性别效应。在所有 OMS 中，在年龄校正后，只有 OMS 严重程度的小效应仍然存在。测量 γδ T 细胞激活标志物[人类白细胞抗原 D 相关（HLA-DR）]、成熟标志物（CD45RA、CD45RO）或细胞内细胞因子染色[白细胞介素（IL）-4、干扰素（IFN）-γ]均无法区分 OMS 和 NIND 组。在七种 OMS 免疫疗法/组合中，没有一种能显著改变总 CSF γδ T 细胞或亚群的频率。在 OIND 中，其他副肿瘤性疾病[神经元核抗体（ANNA）-1、PCA-1、畸胎瘤相关综合征]、小脑共济失调（感染后、共济失调-毛细血管扩张症）、急性播散性脑脊髓炎、神经莱姆病和脑炎的单个样本 CSF γδ T 细胞频率<10%。本研究为儿科人群的 CSF γδ T 细胞提供了新的见解。尽管它们在 CSF 中的作用尚不清楚，但年龄的负相关、对免疫疗法的抵抗力以及我们为 NIND 设定的年龄截止值参考是设计未来儿科研究的重要发现。
