Adoptive Transfusion of Tolerance Dendritic Cells Prolongs the Survival of Cardiac Allograft: a Systematic Review of 44 Basic Studies in Mice

Background And Objective: Tolerogenic DCs (Tol-DCs), a group of cells with imDC phenotype, can stably induce T cells low-reactivity and immune tolerance. We systematically reviewed the adoptive transfusion of Tol-DCs induced by different ways to prolong cardiac allograft survival and its possible mechanism.

Method: MEDLINE (1966 to March 2011), EMbase (1980 to March 2011), and ISI (inception to March 2011) were searched for identification of relevant studies. We used allogeneic heart graft survival time as endpoint outcome to analyze the effect of adoptive transfusion of Tol-DC on cardiac allograft. By integrating studies' information, we summarized the mechanisms of Tol-DC in prolonging cardiac grafts.

Results: Four methods were used to induce Tol-DC in all of the 44 included studies including gene-modified, drug-intervened, cytokine-induced, and other-derived (liver-derived & spleen-derived) DCs. The results showed that all types of Tol-DC can effectively prolong graft survival, and the average extension of graft survival time for each group was as follows: 22.02 ± 21.9 days (3.2 folds to control group) in the gene modified group, 25.94 ± 16.9 days (4.3 folds) in the drug-intervened groups, 9.00 ± 8.13 days (1.9 folds) in the cytokine-induced group, and 10.69 ± 9.94 days (2.1 folds) in the other-derived group. The main mechanisms of Tol-DCs to prolong graft survival were as follows: (1) induceT-cell hyporeactivity (detected by MLR); (2) reduce the effect of cytotoxic lymphocyte (CTL); (3) promote Th2 differentiation; (4) induce Treg; (5) induce chimerism.

Conclusion: For fully MHC mismatched allogeneic heart transplant recipients of inbred mouse, adoptive transfusion of Tol-DC, which can be gene-modified, drug-intervened, cytokine-induced, spleen-derived or liver-derived, can clearly prolong the survival of cardiac allograft or induce immune tolerance. Gene-modified and drug-induced Tol-DC can prolong graft survival most obviously. Having better reliability and stability than drug-induction, gene-modification is the best way to induce Tol-DCs at present. One-time intravenous infusion of 2 × 10(6) Tol-DC is a simple and feasible way to induce long-term graft survival. Multiple infusions will prolong it but increase the risk and cost. Adoptive transfusion of Tol-DC in conjunction with immunosuppressive agents may also prolong the graft survival time.