Mass cytometry and single cell RNA sequencing analysis of mouse liver transplantation
Masayuki Fujino1,3, Xin Hu1, Weitao Que1, Yifang Shui2, Xiao-Kang Li1.
1Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; 2Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China; 3Research Center for Biosafety, Laboratory Animal and Pathogen Bank, National Institute of Infectious Diseases, Tokyo, Japan
The liver, as a tolerogenic organ with exquisite mechanisms of immune regulation, has high rates of operational tolerance after transplantation, allowing it to maintain its normal function for long periods. The mechanisms underlying this unique hepatic property have not yet been fully delineated. To study the involved mechanisms, we developed a mouse spontaneous liver transplantation model. Here, we performed cytometry by mass cytometry and revealed the distinctive immunological phenotypes of an exhaustion and regulatory CD8 T cells cluster and highly express costimulatory molecules subsets that were preferentially enriched in allogeneic grafts donor livers. We believe that this cluster of CD8 T cells may have played a role in the immune tolerance mechanism of transplantation. Nonparenchymal cells extracted from murine syngeneic grafts and allogeneic grafts donor livers were further revealed by single-cell RNA sequencing. We focused on elucidating the role of immune cells in transplant rejection and tolerance. We found T cells in allograft were more active in cytotoxicity and cytokine secretion. At the other hand, we also found that with the extension of time, T cells gradually exhausted. The well-known co-stimulatory molecule CD86 and CD80 are expressed in CD8 T cell clusters. Based on the above findings, our liver transplantation model has gained some new understanding of immune escape-related cells of transplant immunity.
[1] Spontaneous tolerance
[2] liver allograft