Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Clin Exp Immunol. 2021 Apr;204(1):1-13. doi: 10.1111/cei.13559. Epub 2020 Dec 27.
Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti-neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (T ) in the pathogenesis of AIN in childhood. T have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting T , activated T and non-suppressive T . The frequency of activated T (CD4 CD25 FoxP3 CD45RA T cells) as well as that of total T (CD4 CD25 FoxP3 T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vβ repertoire of CD4 T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vβ families in T and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vβ family in conventional and T was significantly higher than that reported in control subjects. When the preference between T and conventional T cells in each TCR-Vβ family was individually compared, different use was prominently observed in the TCR-Vβ 9 family in patients with AIN. These results suggest that the quantitative abnormalities of T and the skew of the TCR-Vβ repertoire in CD4 T cells, including T and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.
儿童自身免疫性中性粒细胞减少症 (AIN) 的特征是慢性中性粒细胞减少和抗中性粒细胞抗体阳性，导致中性粒细胞过度破坏。在这项研究中，我们研究了调节性 T 细胞 (T) 在儿童 AIN 发病机制中的作用。根据 CD45RA 和叉头框蛋白 3 (FoxP3) 的表达，T 细胞可分为三个亚群：静息 T 细胞、活化 T 细胞和非抑制性 T 细胞。AIN 患者外周血中活化 T(CD4 CD25 FoxP3 CD45RA T 细胞)和总 T(CD4 CD25 FoxP3 T 细胞)的频率明显降低。对 CD4 T 细胞 T 细胞受体 (TCR)-Vβ 谱系的分析表明，AIN 患者与年龄匹配的对照组相比，存在明显的偏向性使用。就 T 细胞亚群而言，AIN 患者 T 和常规 T 细胞中 24 个 TCR-Vβ 家族中的 4 个和 1 个家族的使用增加。AIN 患者中常规和 T 细胞中 TCR-Vβ 家族出现偏向性使用的患者数量明显高于对照组。当单独比较每个 TCR-Vβ 家族中 T 和常规 T 细胞之间的偏好时，在 AIN 患者中 TCR-Vβ9 家族中观察到明显的不同使用。这些结果表明，T 和包括 T 和常规 T 细胞在内的 CD4 T 细胞 TCR-Vβ 谱系的定量异常可能与抗人中性粒细胞抗原反应性 T 细胞克隆的自身抗体产生有关。
