Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Humoral immunity-mediated chronic rejection in liver transplantation is associated with predominant IL-10 expression
Academic Editor: Yong Zhao
Chronic rejection is a major cause of graft dysfunction and retransplantation after liver allotransplantation. Recent studies have implicated humoral response in this chronic rejection reaction. However, the manner in which humoral response is activated has not been fully investigated. In the present study, we address this question using our previously established chronic allograft liver rejection model induced by low-dose immunosuppressive cyclosporine (CsA) following Dark Agouti (DA) to Brown Norway (BN) liver transplantation. High-level donor-specific antibodies (IgG1 isotype), C4d deposition and histological graft damage indicated the involvement of humoral rejection in this chronic rejection reaction. In vitro assay showed that alloantibodies from pre-sensitized BN recipients induced apoptosis of bile ductal cells isolated from donor livers and the production of pro-fibrosis factors (TGF-beta, PDGF and FGF). Statistical analysis showed that the serum level of IL-10 was positively correlated with that of donor-specific antibodies (IgG1 isotype). Blockade of IL-10 in vivo down-regulated the level of donor-specific antibodies and ameliorated the outcome of chronic rejection. This suggests that humoral response in chronic allograft liver rejection is associated with Th2 type cytokine IL-10 and that Th2 response might promote chronic rejection by inducing a humoral response.