Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8+regulatory T cells in a rat tolerant liver transplantation model

Han Li; Lin Zhou; Ya-Nan Jia; Ruo-Ling Wang; Ji-Qiao Zhu; Xin-Xue Zhang; Wen-Li Xu; Shao-Yan Liu; Qiang He; Xian-Liang Li

doi:10.1016/j.trim.2021.101508

Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8⁺regulatory T cells in a rat tolerant liver transplantation model

Transpl Immunol. 2022 Feb:70:101508. doi: 10.1016/j.trim.2021.101508. Epub 2021 Nov 27.

Authors

Affiliations

¹ Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, China.
³ Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: lixianliangbjcy@126.com.

PMID: 34843936
DOI: 10.1016/j.trim.2021.101508

Abstract

Background: Tolerance is more easily induced in liver transplant models than in other organs; CD8⁺CD45RC^lowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8⁺CD45RC^lowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8⁺CD45RC^lowTregs effect remains to be investigated.

Methods: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8⁺CD45RC^lowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR).

Results: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8⁺CD45RC^lowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8⁺CD45RC^lowTregs were positively associated with the frequency of pDCs (P = 0.001, r² = 0.775). The protein and mRNA expression of IL-10 and TGF-β in the allograft group were increased, possibly being responsible for tolerance induction.

Conclusion: CD8⁺CD45RC^lowT cells interact with pDCs through the induction of IL-10 and TGF-β expression and are responsible for inducing immune tolerance in rat liver transplantation.

Keywords: CD8(+)CD45RC(low)T cells; Dendritic cells; Immune tolerance; Liver transplantation; Regulatory T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Dendritic Cells / metabolism
Graft Rejection
Liver Transplantation*
Rats
T-Lymphocytes, Regulatory*