Wallin Elizabeth F, Hill Danika L, Linterman Michelle A, Wood Kathryn J
Transplant Research Immunology Group, Nuffield Department Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Lymphocyte Signalling ISP, Babraham Institute, Cambridge, United Kingdom.
Front Immunol. 2018 May 31;9:1184. doi: 10.3389/fimmu.2018.01184. eCollection 2018.
T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients.
Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation. Living-donor recipients received a week of tacrolimus prior to kidney transplantation. Deceased-donor recipients served as controls, as tacrolimus was not administered until after the transplant operation. Flow cytometry was used to compare LN and circulating cell subsets.
The calcineurin inhibitor (CNIs) tacrolimus specifically suppresses both LN Tfh cells and circulating Tfh cells, but not their regulatory counterparts or other CD4 T cell subsets.
Our findings suggest that CNIs may have a more important role in the prevention of antibody formation than previously understood and, therefore, have potential for antibody-associated conditions in which aberrant Tfh function has been implicated in disease.
滤泡辅助性T细胞（Tfh）是生发中心反应中产生抗体的B细胞的关键参与者。在抗体形成与疾病相关的情况下，如移植排斥和自身免疫性疾病，针对Tfh细胞的治疗策略很重要。我们研究了免疫抑制剂他克莫司对移植受者中人类Tfh细胞分化和功能的影响。
在器官植入前，从61名移植受者中获取配对的血液和淋巴结（LN）样本。活体供体受者在肾移植前接受一周的他克莫司治疗。已故供体受者作为对照，因为他克莫司直到移植手术后才给药。采用流式细胞术比较淋巴结和循环细胞亚群。
钙调神经磷酸酶抑制剂（CNIs）他克莫司特异性抑制淋巴结Tfh细胞和循环Tfh细胞，但不抑制其调节性对应细胞或其他CD4 T细胞亚群。
我们的研究结果表明，CNIs在预防抗体形成方面可能比以前认为的具有更重要的作用，因此，对于Tfh功能异常与疾病相关的抗体相关病症具有潜在应用价值。
