BACKGROUND: We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, it remains unknown whether CD47 incompatibility also contributes to the rejection of non-hematopoietic xenografts. AIMS: Here, we investigated the role of CD47 in preventing macrophage-mediated rejection of thymic epithelial cells in a mouse model of thymic transplantation across the CD47 barrier. METHODS: Wild-type (WT) and CD47 KO mice were thymectomized and treated with T cell-depleting mAbs, and implanted with fetal thymus from syngeneic WT or CD47 KO donors. RESULTS: Transplantation of CD47 KO mouse thymus led to T cell recovery in thymectomized, T cell-depleted WT mice. Similar to the control WT mouse thymic grafts, CD47 KO mouse thymic grafts showed a normal distribution of thymocyte subsets, and almost all of the thymocytes were recipient origin. Furthermore, histological analysis confirmed long-term survival of CD47 KO mouse thymic epithelial cells in WT mouse recipients. CONCLUSIONS: These results demonstrate that, unlike hematopoietic cells, CD47 KO mouse thymus can survive and function in WT mice. Furthermore, our data implicate that the role of CD47 in xenograft rejection may differ for different types of xenografts, and that CD47 incompatibility is unlikely to impede thymic xenotransplantation, a potential approach to inducing xenotolerance, by triggering macrophage-mediated rejection.
BACKGROUND: We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, it remains unknown whether CD47 incompatibility also contributes to the rejection of non-hematopoietic xenografts. AIMS: Here, we investigated the role of CD47 in preventing macrophage-mediated rejection of thymic epithelial cells in a mouse model of thymic transplantation across the CD47 barrier. METHODS: Wild-type (WT) and CD47 KO mice were thymectomized and treated with T cell-depleting mAbs, and implanted with fetal thymus from syngeneic WT or CD47 KO donors. RESULTS: Transplantation of CD47 KO mouse thymus led to T cell recovery in thymectomized, T cell-depleted WT mice. Similar to the control WT mouse thymic grafts, CD47 KO mouse thymic grafts showed a normal distribution of thymocyte subsets, and almost all of the thymocytes were recipient origin. Furthermore, histological analysis confirmed long-term survival of CD47 KO mouse thymic epithelial cells in WT mouse recipients. CONCLUSIONS: These results demonstrate that, unlike hematopoietic cells, CD47 KO mouse thymus can survive and function in WT mice. Furthermore, our data implicate that the role of CD47 in xenograft rejection may differ for different types of xenografts, and that CD47 incompatibility is unlikely to impede thymic xenotransplantation, a potential approach to inducing xenotolerance, by triggering macrophage-mediated rejection.
Authors: Shin Yamamoto; John M Lavelle; Parsia A Vagefi; Hitoshi Arakawa; Emma Samelson-Jones; Shannon Moran; Katsuhito Teranishi; Chisako Kamano; Jay Fishman; Michel Awwad; David M Neville; Akira Shimizu; Megan Sykes; David H Sachs; Kazuhiko Yamada Journal: Transplantation Date: 2005-12-27 Impact factor: 4.939
Authors: Hui Wang; Maria Lucia Madariaga; Shumei Wang; Nico Van Rooijen; Per-Arne Oldenborg; Yong-Guang Yang Journal: Proc Natl Acad Sci U S A Date: 2007-08-15 Impact factor: 11.205
Authors: Andrew S Flies; Nicholas B Blackburn; Alan Bruce Lyons; John D Hayball; Gregory M Woods Journal: Front Immunol Date: 2017-05-03 Impact factor: 7.561