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_regs) in the pathogenesis of AIN in childhood. T_regs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting T_regs, activated T_regs and non‐suppressive T_regs. The frequency of activated T_regs (CD4⁺CD25⁺FoxP3^highCD45RA⁻ T cells) as well as that of total T_regs (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_regs 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_regs was significantly higher than that reported in control subjects. When the preference between T_regs 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_regs and the skew of the TCR‐Vβ repertoire in CD4⁺ T cells, including T_regs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen‐reactive T cell clone.

中文翻译：

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自身免疫性中性粒细胞减少症患儿可能涉及调节性 T 细胞异常和 TCR 库的变化使用

儿童自身免疫性中性粒细胞减少症（AIN）的特点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，我们调查了调节性 T 细胞 (T _regs ) 在儿童 AIN 发病机制中的作用。根据 CD45RA 和叉头盒蛋白 3 (FoxP3) 的表达，将T _regs分为三个亚群：静息 T _regs、活化 T _regs和非抑制性 T _regs。激活的 T _regs（CD4 ⁺ CD25 ⁺ FoxP3^高CD45RA ^- T 细胞）的频率以及总 T的频率AIN患者外周血中的_regs（CD4 ⁺ CD25 ⁺ FoxP3 ^{+ T细胞）显着降低。对 CD4 +} T 细胞的 T 细胞受体 (TCR)-Vβ 库的分析显示，与年龄匹配的对照受试者相比，AIN 患者的使用有偏差。关于 T 细胞亚群，在 AIN 患者中，T _regs中 24 个 TCR-Vβ 家族中的四个和常规 T 细胞中的一个使用增加。_{在常规和 T regs}中显示出偏斜使用 TCR-Vβ 家族的 AIN 患者数量显着高于对照组报告的数量。当 T _{regs之间的偏好}并且单独比较了每个 TCR-Vβ 家族中的常规 T 细胞，在 AIN 患者的 TCR-Vβ 9 家族中明显观察到不同的用途。这些结果表明， CD4 ⁺ T 细胞（包括 T _{regs和常规 T 细胞）中 T regs}的数量异常和 TCR-Vβ 库的偏斜可能与通过人中性粒细胞抗原反应性 T 细胞克隆产生自身抗体有关。