Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance

Summary: The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune la...

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Main Authors: Weitao Que, Hisashi Ueta, Xin Hu, Miwa Morita-Nakagawa, Masayuki Fujino, Daisuke Ueda, Nobuko Tokuda, Wenxin Huang, Wen-Zhi Guo, Lin Zhong, Xiao-Kang Li
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223017686
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author Weitao Que
Hisashi Ueta
Xin Hu
Miwa Morita-Nakagawa
Masayuki Fujino
Daisuke Ueda
Nobuko Tokuda
Wenxin Huang
Wen-Zhi Guo
Lin Zhong
Xiao-Kang Li
author_facet Weitao Que
Hisashi Ueta
Xin Hu
Miwa Morita-Nakagawa
Masayuki Fujino
Daisuke Ueda
Nobuko Tokuda
Wenxin Huang
Wen-Zhi Guo
Lin Zhong
Xiao-Kang Li
author_sort Weitao Que
collection DOAJ
description Summary: The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance. Of note, the CD4+/CD8+ T cell ratio remained low, even in the tolerance phase. Furthermore, a PhenoGraph clustering analysis revealed that exhausted CD8+ T cells were the most dominant metacluster in graft-infiltrating lymphocytes (GILs), which highly expressed the costimulatory molecule CD86. The temporal and spatial dynamics of immune cells revealed by high-dimensional analyses enable a fine-grained analysis of GIL subsets, contribute to new insights for the discovery of immunological mechanisms of liver tolerance, and provide potential ways to achieve clinical operational tolerance after liver transplantation.
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spelling doaj.art-d0f85edbc0264675a40c61385981e9642023-09-02T04:32:11ZengElsevieriScience2589-00422023-09-01269107691Temporal and spatial dynamics of immune cells in spontaneous liver transplant toleranceWeitao Que0Hisashi Ueta1Xin Hu2Miwa Morita-Nakagawa3Masayuki Fujino4Daisuke Ueda5Nobuko Tokuda6Wenxin Huang7Wen-Zhi Guo8Lin Zhong9Xiao-Kang Li10Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Anatomy, Dokkyo Medical University, Tochigi 321-0293, JapanDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Oral Medicine Research Center, Fukuoka Dental College, Fukuoka 814-0175, JapanManagement Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Tokyo 162-8640, JapanDivision of Hepato-Pancreato-Biliary Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8303, JapanDepartment of Anatomy, Dokkyo Medical University, Tochigi 321-0293, JapanDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Corresponding authorDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Corresponding authorDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan; Corresponding authorSummary: The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance. Of note, the CD4+/CD8+ T cell ratio remained low, even in the tolerance phase. Furthermore, a PhenoGraph clustering analysis revealed that exhausted CD8+ T cells were the most dominant metacluster in graft-infiltrating lymphocytes (GILs), which highly expressed the costimulatory molecule CD86. The temporal and spatial dynamics of immune cells revealed by high-dimensional analyses enable a fine-grained analysis of GIL subsets, contribute to new insights for the discovery of immunological mechanisms of liver tolerance, and provide potential ways to achieve clinical operational tolerance after liver transplantation.http://www.sciencedirect.com/science/article/pii/S2589004223017686ImmunologyCell biologyOrganizational aspects of cell biology
spellingShingle Weitao Que
Hisashi Ueta
Xin Hu
Miwa Morita-Nakagawa
Masayuki Fujino
Daisuke Ueda
Nobuko Tokuda
Wenxin Huang
Wen-Zhi Guo
Lin Zhong
Xiao-Kang Li
Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
iScience
Immunology
Cell biology
Organizational aspects of cell biology
title Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
title_full Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
title_fullStr Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
title_full_unstemmed Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
title_short Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
title_sort temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
topic Immunology
Cell biology
Organizational aspects of cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004223017686
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