Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom.
Curr Opin Immunol. 2011 Oct;23(5):648-54. doi: 10.1016/j.coi.2011.06.005.
Chronic allograft dysfunction (CAD) in solid organ transplantation is a principal cause of patient morbidity and late allograft loss. The pathogenesis of CAD is largely secondary to chronic damage by the adaptive immune system and long-term immunosuppression. Manipulating these factors may be possible with the use of regulatory T cells (Treg), which have the ability to suppress specific immune responses and therefore potentially remove the need for immunosuppressive drugs. Studies of CAD in experimental models have demonstrated the capacity for both mouse and human Treg cellular therapy to prevent the development of some manifestations of CAD. Furthermore, a role for Treg has been demonstrated in clinically tolerant transplant patients. Certain immunosuppressive therapies are also proving to be 'Treg friendly' and may be helpful in promoting Treg while maintaining other immunosuppressive activity. With this in mind, monitoring for biomarkers of operational tolerance with tailored immunosuppressive therapy or controlled weaning in conjunction with Treg cellular therapy may be a useful strategy to pursue.
实体器官移植中的慢性移植物功能障碍 (CAD) 是患者发病率和晚期移植物丢失的主要原因。CAD 的发病机制主要继发于适应性免疫系统的慢性损伤和长期免疫抑制。通过使用具有抑制特定免疫反应能力的调节性 T 细胞 (Treg) ，可能有可能操纵这些因素，从而可能不需要免疫抑制药物。在实验模型中对 CAD 的研究表明，小鼠和人类 Treg 细胞治疗均有能力预防某些 CAD 表现的发展。此外，在临床上耐受移植的患者中也证明了 Treg 的作用。某些免疫抑制疗法也被证明对 Treg 友好，并且在维持其他免疫抑制活性的同时促进 Treg 可能会有所帮助。考虑到这一点，监测具有定制免疫抑制疗法的操作性耐受的生物标志物，或与 Treg 细胞治疗一起进行受控脱机，可能是一种有用的策略。
