首页 | 本学科首页   官方微博 | 高级检索  
     


IL‐2 therapy preferentially expands adoptively transferred donor‐specific Tregs improving skin allograft survival
Authors:Kulachelvy Ratnasothy  Jacintha Jacob  Sim Tung  Dominic Boardman  Robert Ian Lechler  Alberto Sanchez-Fueyo  Marc Martinez‐Llordella  Giovanna Lombardi
Abstract:
Regulatory T cells (Tregs) have unique immunosuppressive properties and are essential to ensure effective immunoregulation. In animal models, Tregs have been shown to prevent autoimmune disorders and establish transplantation tolerance. Therefore, the prospect of harnessing Tregs, either by increasing their frequency or by conferring allospecificity, has prompted a growing interest in the development of immunotherapies. Here, employing a well‐established skin transplant model with a single major histocompatibility complex mismatch, we compared the therapeutic efficacy of adoptively transfer Treg with or without donor specificity and the administration of IL‐2 to promote in vivo expansion of Treg. We showed that IL‐2 treatment preferentially enhances the proliferation of the allospecific Tregs adoptively transferred in an antigen‐dependent manner. In addition, donor‐specific Tregs significantly increased the expression of regulatory‐related marker, such as CTLA4 and inducible costimulator (ICOS), in the skin allograft and draining lymph nodes compared to endogenous and polyclonal transferred Tregs. Importantly, by combining IL‐2 with donor‐specific Tregs, but not with polyclonal Tregs, a synergistic effect in prolonging skin allograft survival was observed. Altogether, our data suggest that this combination therapy could provide the appropriate conditions to enhance the immunoregulation of alloimmune responses in clinical transplantation.
Keywords:antigen presentation/recognition  basic (laboratory) research/science  graft survival  immune regulation  immunobiology  immunosuppression/immune modulation  organ transplantation in general  T cell biology  tolerance  translational research/science
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号