Baan Carla C, de Graav Gretchen N, Boer Karin
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, Room Nc508, 3000 CA Rotterdam, The Netherlands.
Curr Transplant Rep. 2014;1(3):166-172. doi: 10.1007/s40472-014-0019-4.
Antibody-mediated, humoral rejection has been recognized as a common cause of transplant dysfunction and is responsible for 30-50 % of failed allografts. The production of antibody is dependent on instructions from memory CD4+ T helper cells that interact with antigen-specific B cells. Recently, a specialized T-cell subset has been identified-T follicular helper (Tfh) cells-which support activated B cells via interleukin (IL)-21 after binding to the IL-21 receptor expressed by these B cells. Therefore, neutralizing the IL-21 pathway will selectively inhibit the allogeneic IL-21-driven Tfh- and B-cell functions. However, little is known of the role of Tfh cells in alloreactivity. In this review, we debate the role of Tfh cells in B-cell-mediated allogeneic responses by discussing their mechanisms of actions. In addition, we speculate about the use of agents that intervene in Tfh-B-cell interaction and consequently prevent or treat antibody-mediated rejection in patients after transplantation.
抗体介导的体液排斥已被公认为移植功能障碍的常见原因，并且在30%至50%的移植失败中起作用。抗体的产生依赖于记忆性CD4+辅助性T细胞与抗原特异性B细胞相互作用所发出的指令。最近，一种特殊的T细胞亚群——滤泡辅助性T（Tfh）细胞——已被识别出来，它在与这些B细胞表达的白细胞介素（IL）-21受体结合后，通过IL-21支持活化的B细胞。因此，中和IL-21途径将选择性地抑制同种异体IL-21驱动的Tfh细胞和B细胞功能。然而，关于Tfh细胞在同种异体反应中的作用知之甚少。在这篇综述中，我们通过讨论Tfh细胞的作用机制，探讨其在B细胞介导的同种异体反应中的作用。此外，我们推测干预Tfh细胞与B细胞相互作用从而预防或治疗移植后患者抗体介导排斥反应的药物的应用。
