Lin Shaofen, Hou Lele, Liu Su, Wang Jian, Chen Qihui, Zhang Bihong, Xue Hongman, Huang Junbin, Chen Chun
a Department of Paediatric Hematopathy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou , Guangdong , China.
b Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University , Shenzhen , Guangdong , China.
Pediatr Hematol Oncol. 2019 May;36(4):198-210. doi: 10.1080/08880018.2019.1621968. Epub 2019 Jul 9.
The pathogenesis of aplastic anemia (AA) in children is not clear. This study was conducted to investigate the changes in the proportion and function of regulatory T cells (Tregs) in pediatric AA. The proportion of Tregs, mRNA levels of transcription factors, and concentrations of cytokines were measured by flow cytometry, reverse transcription-PCR, and enzyme-linked immunosorbent assay, respectively. Tregs were co-cultured with effector T cells (Teff) to evaluate the function of Tregs. The proportion of Tregs after immunosuppressive therapy (IST) in pediatric AA was monitored dynamically. Compared to the control, the proportions of Tregs in peripheral blood and bone marrow lymphocytes of the untreated AA group were lower (1.31% ± 0.73% vs. 3.16% ± 0.92%, 1.49% ± 0.81% vs. 3.06% ± 0.82%, respectively, < 0.001). The mRNA levels of FOXP3 and STAT3 in the AA group were lower ( = 0.014; < 0.001). However, the mRNA levels of T-BET did not significantly differ between groups. The concentration of interferon-γ and interleukin-17 in the AA group were higher ( = 0.004; = 0.003), whereas the concentration of decreased ( = 0.044). The immunosuppressive function of Tregs was impaired in the AA group. After IST, the proportion of Tregs was significantly lower than that in the control. The proportion of Tregs at the time of diagnosis in the nonresponsive group was lower than that in the responsive group, but the difference was not significant. Treg levels were significantly decreased and were functionally impaired at the time of diagnosis of pediatric AA. However, there was no significant change in Tregs at the resolution of AA.
儿童再生障碍性贫血（AA）的发病机制尚不清楚。本研究旨在探讨小儿AA中调节性T细胞（Tregs）比例及功能的变化。分别采用流式细胞术、逆转录聚合酶链反应和酶联免疫吸附测定法检测Tregs比例、转录因子的mRNA水平及细胞因子浓度。将Tregs与效应T细胞（Teff）共培养以评估Tregs的功能。动态监测小儿AA免疫抑制治疗（IST）后Tregs的比例。与对照组相比，未治疗的AA组外周血和骨髓淋巴细胞中Tregs的比例较低（分别为1.31%±0.73%对3.16%±0.92%，1.49%±0.81%对3.06%±0.82%，P均<0.001）。AA组中FOXP3和STAT3的mRNA水平较低（P = 0.014；P<0.001）。然而，各组间T - BET的mRNA水平无显著差异。AA组中干扰素 - γ和白细胞介素 - 17的浓度较高（P = 0.004；P = 0.003），而白细胞介素 - 10的浓度降低（P = 0.044）。AA组中Tregs的免疫抑制功能受损。IST后，Tregs的比例显著低于对照组。无反应组诊断时Tregs的比例低于反应组，但差异无统计学意义。小儿AA诊断时Treg水平显著降低且功能受损。然而，AA缓解时Tregs无显著变化。
