Temporal and spatial dynamics of immune cells in spontaneous liver transplant tolerance
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
Affiliations
Weitao Que
Department 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, China
Hisashi Ueta
Department of Anatomy, Dokkyo Medical University, Tochigi 321-0293, Japan
Xin Hu
Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan
Miwa Morita-Nakagawa
Division 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, Japan
Masayuki Fujino
Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Daisuke Ueda
Division of Hepato-Pancreato-Biliary Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8303, Japan
Nobuko Tokuda
Department of Anatomy, Dokkyo Medical University, Tochigi 321-0293, Japan
Wenxin Huang
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Wen-Zhi Guo
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Corresponding author
Lin Zhong
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Corresponding author
Xiao-Kang Li
Department 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 author
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.
