한빛사논문
- 조회1,376
Abstract
Hidekazu Nishikii1,2*, Byung-Su Kim1*, Yasuhisa Yokoyama2, Yan Chen1,3, Jeanette Baker1, Antonio Pierini1, Maite Alvarez1, Melissa Mavers4, Kristina Maas-Bauer1, Yuqiong Pan1, Shigeru Chiba2 and Robert S. Negrin1
1Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA; 2Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan; 3Central South Univeristy Xiangya Hospital, Department of Hematology, Changsha, China; 4Department of Pediatrics, Divisions of Hematology/Oncology and Stem Cell Transplantation and Regenerative Medicine, Stanford University, Stanford, CA.
Corresponding Author : Robert S. Negrin, MD
Professor of Medicine, Chief, Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University
Abstract
CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. In this study, we comprehensively analyzed the immunophenotype of Treg after DR3 signal activation, demonstrating that DR3 activated Treg (DR3-Treg) had an activated/mature phenotype. Furthermore, the CD25+Foxp3+ subpopulation in DR3-Treg showed stronger suppressive effects in vivo. Prophylactic treatment of αDR3 to recipient mice expanded recipient derived Treg and reduced the severity of GVHD, whereas DR3 activation in mice with ongoing GVHD further promoted donor T cell activation/proliferation. These data suggest that the function of DR3 signaling was highly dependent on the activation status of the T cells. In conclusion, our data demonstrated that DR3 signaling affects the function of Treg and T cell activation after alloantigen exposure in a time-dependent manner. These observations provide important information for future clinical testing using human DR3 signal modulation and highlight the critical impact of the state of T cell activation on clinical outcomes following activation of DR3.
논문정보
- Research article
- 2016년 10월 (BRIC 등록일 2016-10-25)
- 국외 연구진
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