Zhang Ke, Sun Yan-Ling, Yang Fan, Shi Yan-Chao, Jin Lei, Liu Zhen-Wen, Wang Fu-Sheng, Shi Ming
Treatment and Research Center for Infectious Disease, 302 Military Hospital of China, Peking University Teaching Hospital, Beijing, China.
Research Center for Liver transplantation, Beijing 302 Hospital, Beijing, China.
Transpl Immunol. 2018 Apr;47:32-36. doi: 10.1016/j.trim.2018.01.003. Epub 2018 Feb 2.
Circulating CD4CXCR5 T follicular helper cells (cTfh) have been demonstrated to be involved in B cell-mediated systemic autoimmune diseases and alloreactive responses following kidney transplantation; however, whether cTfh cells are involved in alloreactive responses after liver transplantation (LT) remains unclear. Our present study aimed to investigate the characteristics of cTfh, as well as CXCR3CCR6Tfh1, CXCR3CCR6Tfh2, and CXCR3CCR6Tfh17 subsets in liver allograft recipients. A total of 30 liver transplant recipients were enrolled in this study. The frequencies of cTfh, Tfh1, Tfh2, and Tfh17 subsets, and interleukin (IL)-21-producing Tfh cells in the circulating blood were analyzed by flow cytometry. The capacity of cTfh cells to help B cells differentiate into plasmablasts was determined one day before and one month after LT. The results revealed that the frequency of cTfh cells remained unaltered before and after LT. However, the frequency of the cTfh subsets (e.g., Tfh1 and Tfh2 cells) and B cells were reduced one month after LT. Functionally, the capacity of Tfh cells to produce IL-21 was reduced one month after LT. In addition, cTfh cells exhibited the capacity to help B cells differentiate into plasmablasts in an IL-21-dependent manner in vitro, which was reduced after LT, despite the unaltered production of IgM and IgG by plasmablasts. Thus, our data suggest that cTfh cells may be involved in alloreactive responses following LT via helping B cells differentiate into plasmablasts and plasma cells.
循环CD4⁺CXCR5⁺滤泡辅助性T细胞（cTfh）已被证明参与B细胞介导的系统性自身免疫性疾病以及肾移植后的同种异体反应；然而，cTfh细胞是否参与肝移植（LT）后的同种异体反应仍不清楚。我们目前的研究旨在调查肝移植受者中cTfh以及CXCR3⁺CCR6⁺Tfh1、CXCR3⁺CCR6⁺Tfh2和CXCR3⁺CCR6⁺Tfh17亚群的特征。本研究共纳入30名肝移植受者。通过流式细胞术分析循环血液中cTfh、Tfh1、Tfh2和Tfh17亚群以及产生白细胞介素（IL）-21的Tfh细胞的频率。在肝移植前一天和移植后一个月测定cTfh细胞帮助B细胞分化为成浆细胞的能力。结果显示，肝移植前后cTfh细胞的频率保持不变。然而，肝移植后一个月，cTfh亚群（如Tfh1和Tfh2细胞）和B细胞的频率降低。在功能上，肝移植后一个月Tfh细胞产生IL-21的能力降低。此外，尽管成浆细胞产生的IgM和IgG没有改变，但体外cTfh细胞表现出以IL-21依赖的方式帮助B细胞分化为成浆细胞的能力，肝移植后该能力降低。因此，我们的数据表明，cTfh细胞可能通过帮助B细胞分化为成浆细胞和浆细胞参与肝移植后的同种异体反应。
