TY - JOUR AU - Lai, Xingqiang AU - Yao, Zhongpeng AU - Ning, Fen AU - Zhang, Lei AU - Fang, Jiali AU - Li, Guanghui AU - Xu, Lu AU - Xiong, Yunyi AU - Liu, Luhao AU - Chen, Rongxin AU - Ma, Junjie AU - Chen, Zheng PY - 2020 TI - Blockade of OX40/OX40L pathway combined with ethylene-carbodiimide-fixed donor splenocytes induces donor-specific allograft tolerance in presensitized recipients JF - Annals of Translational Medicine; Vol 8, No 4 (February 29, 2020): Annals of Translational Medicine (Focus on "Intrauterine Adhesion") Y2 - 2020 KW - N2 - Background: Memory T cells (Tms) are the major barrier preventing long-term allograft survival in presensitized transplant recipients. The OX40/OX40L pathway is important in the induction and maintenance of Tms. Methods: In this study, we added anti-OX40L mAb to ethylene-carbodiimide-fixed donor splenocytes (ECDI-SPs)—a method which is effective in inducing allograft tolerance in non-presensitized mouse heart transplant model. Recipient mice received heart transplantation after 6 weeks of donor skin presensitization and were treated with anti-OX40L mAb, ECDI-SPs or anti-OX40L mAb + ECDI-SPs, respectively. Results: Our data showed that the combination of ECDI-SPs and anti-OX40L mAb induced donor- specific tolerance in skin-presensitized heart transplant recipients, with the mechanism for this being associated with suppression of Tms and upregulation of CD4 + CD25 + Foxp3 + T regulatory cells (Tregs). Importantly, CD25 + T-cell depletion in the combined therapy-treated recipients broke the establishment of allograft tolerance, whereas adoptive transfer of presensitization-derived T cells into tolerant recipients suppressed Tregs expansion and abolished established tolerance. Conclusions: Blockade of OX40/OX40L pathway in combination with ECDI-SPs appears to modulate the Tms/Tregs imbalance so as to create a protective milieu and induce graft tolerance in presensitized recipients. UR - https://atm.amegroups.org/article/view/34805