Galectin-1-induced tolerogenic dendritic cells combined with apoptotic lymphocytes prolong liver allograft survival

Abstract

Donor-derived tolerogenic dendritic cells (DCs) and apoptotic lymphocytes (ALs) are practical tools for controlling rejection after transplantation by targeting direct and indirect allorecognition pathways, respectively. To date, few studies have investigated the combination of donor-derived tolerogenic DCs and ALs infusion in organ transplantation protection. In the present study, we generated galectin-1-induced tolerogenic DCs (DC_gal-1s) and ultraviolet irradiation-induced ALs with stable immune characteristics in vitro and potential immune regulatory activity in vivo. A rat model of acute liver transplant rejection was established, and the intrinsic tolerogenic profiles associated with the short-term alleviation of rejection and the long-term maintenance of tolerance in the absence of immunosuppressive drugs were evaluated. The DC_gal-1-AL treatment prolonged allograft survival more significantly than a transfusion of DC_gal-1s or ALs alone. This benefit was associated with CD4⁺ Treg cell expansion and decreased interferon (IFN)-γ⁺ T cell levels. Moreover, DC_gal-1-AL treatment led to different cytokine/chemokine changes in the allograft and peripheral blood, that indicated an alleviation of local and systemic inflammation on day 7 post-transplantation. TGF-β1 and TGF-β2 were significantly increased in the long-term surviving allografts after DC_gal-1-AL treatment. Our results indicate that the combination of DC_gal-1s with ALs effectively prolongs liver allograft survival and represents a novel therapeutic strategy for liver transplant rejection.

Keywords: Apoptotic lymphocyte; Dendritic cells; Galectin-1; Transplantation.