Immune tolerance induced by RelB short-hairpin RNA interference dendritic cells in liver transplantation.

BACKGROUND

The induction of specific immune tolerance for alloantigen is the best method for solving transplant rejection. We have previously reported T-cell tolerance induced by RNA interference (RNAi) RelB dendritic cells (DCs), supporting the possibility of immunologic tolerance in liver transplantation.

METHODS

A stable model of acute rejection was established in Lewis (RT11) rats that had received a liver graft from dark agouti-RT1a rats. To evaluate the immune tolerance of DCs of different maturity, the rats were randomly assigned to four groups (12 donor/recipient pairs): (1) control-DC group, recipient rats without preinjection; (2) RelB short hairpin (sh)RNAi-DC group, recipient rats with preinjection of tolerogenic DCs by way of RelB silencing; (3) imDC group, recipient rats with preinjection of immature DCs; and (4) lipopolysaccharide-DC group, recipient rats with preinjection of mature DCs. The immune tolerance of the grafts was evaluated by liver function tests (aspartate transaminase, total bilirubin), cytokines (interleukin [IL]-2, IL-4, IL-10 and interferon-γ), and histopathologic examination during the 2 wk after transplantation. The survival time of the rats was also observed.

RESULTS

Compared with the other three groups, the graft survival time was significantly prolonged in the RelB shRNAi-DC group. In addition, RelB shRNAi-DCs resulted in the reduced secretion of IL-2 and interferon-γ and increased levels of IL-10 and IL-4. The symptoms of rejection were obviously alleviated in the RelB shRNAi-DC group, and the rejection activity index was still reduced after 2 wk.

CONCLUSIONS

Injection of RelB-silenced DCs contributed to the reduced incidence of graft rejection and prolonged the graft survival time. The potential mechanisms involved the regulation and induction of immune-incompetent T cell by DCs.