Inhibiting cardiac allograft rejection with interleukin-35 therapy combined with decitabine treatment in mice.

BACKGROUND

Regulatory T (Treg) cells play a pivotal role in the maintenance of transplantation tolerance. It is of great interest to induce allograft tolerance mediated by regulatory CD4(+)CD25(+) T cells.

METHODS

Here we investigated the effect of hydrodynamic IL-35-expressing plasmid injection in combination with a methyltransferase inhibitor (decitabine) on immune function and transplantation tolerance in mice.

RESULTS

We showed that IL-35 and decitabine stimulated the proliferation of CD4(+)CD25(+) Tregs and suppressed CD8(+) T cell proliferation in an allogenic mixed lymphocyte culture in vitro. IL-35 gene therapy and decitabine administration prolonged the survival of the transplanted heart in the heterotopic abdominal heart transplantation model in mice.

CONCLUSIONS

The possible mechanism through which IL-35 and decitabine treatment increased the survival of graft tissues is to enhance the proliferation of CD4(+)CD25(+) Treg cells and suppress the generation and function of effector T cells. Thus, IL-35 gene therapy combined with decitabine provides a novel approach to induce transplantation tolerance.