Prevention of Acute and Chronic Allograft Rejection by Combinations of Tolerogenic Dendritic Cells

Abstract

It is well known that adoptive transfer of donor‐derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)‐derived MMC‐DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T‐cell apoptosis, decreasing IL‐2 and IL‐12 secretion, and increasing regulatory T‐cell numbers and IL‐10 secretion. Furthermore, anti‐CD154 monoclonal antibody (mAb) treatment combined with donor‐derived MMC‐DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c × C57BL/6) derived MMC‐DC were injected together with anti‐CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1‐derived tolerogenic DC have a synergistic effect on induction and maintenance of T‐cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice.

IDO-Competent-DCs Induced by IFN-γ Attenuate Acute Rejection in rat Liver Transplantation

“…Donor-derived DCs were thought to reduce acute allograft rejection, but could not prevent the infiltration of inflammatory cells and fibrosis in the graft [9]. Donor and F1-derived DCs acted synergistically to induce immune tolerance and inhibit both acute and chronic transplant rejection in mice [9].…”

“…The generation of regulatory T cells by injecting tolerogenic dendritic cells (DCs) has been investigated by several groups [3,9,10] and tolerogenic DC therapy was recently used in transplantation [11]. DCs are bone-marrow-derived antigen-presenting cells that have a recognized tolerogenic capability [12] and maintain both central and peripheral tolerance [11].…”

HMGB1 Is Involved in Chronic Rejection of Cardiac Allograft via Promoting Inflammatory-Like mDCs

“…Allograft rejection is induced by DCs presenting donor antigens from the graft to recipient's T lymphocytes. DCs from host taking up, processing and presenting donor's MHC molecules to host's T cells is thought to play a capital role in chronic rejection, and has been recognized as a major threat to longterm graft survival and stable allograft function (8)(9)(10).…”

Expression of HSPA12B in acute cardiac allograft rejection in rats

“…Apoptosis of cardiac myocytes, myocardial inflammation and contractile dysfunction are considered to be the hallmarks of cardiac allograft rejection [5][6][7][8][9]. Recent reports have shown that both innate and adaptive immunity contribute to acute organ transplant rejection, which affects allograft survival a lot [2,10].…”