Yao Xin, Li Chengrong, Yang Jun, Wang Guobing, Li Changgang, Xia Yu
Department of Molecular Immunology, Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, ZunYi Medical College, Shenzhen 518026, China.
Department of Molecular Immunology, Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, ZunYi Medical College, Shenzhen 518026, China.
Blood Cells Mol Dis. 2016 Oct;61:26-36. doi: 10.1016/j.bcmd.2016.06.006. Epub 2016 Jun 18.
This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP).
Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA.
The percentages of TFH cells were significantly elevated in both nITP and cITP compared with controls. RT-PCR revealed significant differences in Bcl-6, c-Maf, Blimp-1, ICOSL, TACI and BAFFR mRNA expression in CD4(+) T or CD19(+) B cells between patients and controls, and further between nITP and cITP, before and after treatment. Moreover, there were significant differences in serum IL-4, IL-21 and BAFF between patients and controls.
The overactivation of TFH cells may contribute to the immunopathogenesis of pediatric ITP. IL-21 and IL-4 serum levels may affect the differentiation of TFH cells in ITP patients. The aberrant balance between BAFFR-BAFF/TACI-BAFF may be a factor that caused the persistent high expression of ICOSL in pediatric cITP, which consequently lead to the over activation of TFH cells in pediatric cITP.
本研究旨在探讨滤泡辅助性T细胞(TFH)在儿童免疫性血小板减少症(ITP)免疫发病机制中的作用,以及初诊ITP(nITP)和儿童慢性ITP(cITP)之间TFH细胞扩增及其调控的差异。
85例ITP患儿和20例年龄匹配的健康对照纳入本研究。采用流式细胞术、逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)分析治疗前后TFH细胞频率及TFH细胞相关调控因子。
与对照组相比,nITP和cITP中TFH细胞百分比均显著升高。RT-PCR显示,患者与对照组之间,以及nITP和cITP之间,治疗前后CD4(+)T细胞或CD19(+)B细胞中Bcl-6、c-Maf、Blimp-1、ICOSL、TACI和BAFFR mRNA表达存在显著差异。此外,患者与对照组之间血清白细胞介素-4(IL-4)、IL-21和B细胞活化因子(BAFF)水平存在显著差异。
TFH细胞过度活化可能参与儿童ITP的免疫发病机制。血清IL-21和IL-4水平可能影响ITP患者TFH细胞的分化。BAFFR-BAFF/TACI-BAFF之间的异常平衡可能是导致儿童cITP中ICOSL持续高表达的一个因素,进而导致儿童cITP中TFH细胞过度活化。