| Institution: | 1. Department of Surgery and Medicine, Transplant International Research Centre (TIRC), Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People''s Republic of China;2. Departments of Medicine, Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;3. Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei City, People''s Republic of China;4. Department of Hemotology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;5. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea |
| Abstract: | Harness of sensitized transplantation remains a clinical challenge particularly in parallel with prolonged cold ischemia time (PCI)-mediated injury. Our present study was to test the role of myeloid-derived suppressor cells (MDSCs) in mouse pre-sensitized transplantation. Our findings revealed that CD11b + Gr1low MDSC was shown to have strong suppressive activity. MDSCs subsets from the tolerated mice exhibited higher suppressive capacities compared with counterparts from naive (untreated) mice. Depletion of Tregs could not affect splenic CD11b + Gr1-low MDSC frequency, but increase peripheral and intragraft CD11b + Gr1-low frequency. Intriguingly, boost of Tregs remarkably caused an increase of CD11b + Gr1-low frequency in the graft, peripheral blood, and spleen. Furthermore, peripheral CD11b + Gr1-low cells were massively accumulated at the early stage when allogeneic immune response was enhanced. Taken together, MDSCs could prevent grafts from PCI-mediated injury independent on Tregs in the pre-sensitized transplant recipients. Utilization of MDSC subset particularly CD11b + Gr1-low might provide a novel insight into improving graft outcome under such clinical scenarios. |
