Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8regulatory T cells in a rat tolerant liver transplantation model.

Background: Tolerance is more easily induced in liver transplant models than in other organs; CD8CD45RCregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8CD45RCTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8CD45RCTregs 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 CD8CD45RCTregs 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 CD8CD45RCTegs 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, CD8CD45RCTregs were positively associated with the frequency of pDCs (P = 0.001, r = 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: CD8CD45RCT 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.