Background and Objective: We recently found that donor semimature dendritic cells (smDCs) could promote skin allograft survival in mice by activating host antigen-specific CD4+CD25+Foxp3+T-regulatory cells (Tregs). In this study, we observe the effects of treating acute rejection with infusion of these donor smDCs in rats liver transplantation.

Methods: DA (donor) and Lewis (recipient) rats were used to establish acute rejection liver transplantation models. After liver transplantation, 10 recipients treated with donor derived smDCs infusion via portal vein were used as experimental group; 10 recipients fed with 1.0mg/kg tacrolimus daily from day 0 to 5 were used as positive control group; 10 untreated recipients were used as negative control group. The survival time of all groups were observed. Histopathological examinations of liver graft were performed on day7, day14, day30, day60 and day90. The levels of CD4+CD25+Foxp3+Tregs, IL-2 and IL-10 of recipients were measured by FCM and ELISA on day7, day14, day21, day30.

Results: The mean survival time of experimental groups was significantly longer than tacrolimus-alone and untreated control group(p<0.01). Evidences of acute rejection were revealed in untreated control group and tacrolimus-alone group by histopathological examination of liver grafts on post-transplant day14 and day30 respectively. Compared with previous two groups, smDCs experimental group showed no obvious signs of rejection within 30 days after transplantation. The IL-2 levels in smDCs experimental group were lower than those in tacrolimus -alone and untreated control groups(p<0.01). However, the IL-10 levels in smDCs experimental group were higher than those in tacrolimus-alone and untreated control group(p<0.01). As a result of FCM, the levels of CD4+CD25+Foxp3+Tregs were also higher than those in tacrolimus -alone and untreated control groups (p<0.05).

Conclusion: Administration of smDCs infusion via portal vein significantly prolonged the survival time of liver transplantation graft. smDCs may be had a key role in activating CD4+CD25+Foxp3+Tregs to induce tolerance. Immunization with donor smDCs may be an effective method of inducing transplantation tolerance, but further evidence-based studies are necessary.

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