Induction of CD4+CD25+ T cells and control of cardiac allograft rejection by CD40/CD40L costimulatory pathway blockade in mice.

Background: Rejection is a major problem in organ transplantation. We speculated that dendritic cells (DCs) with low expression of CD40 may inhibit T-cell responses providing protective effects on organ transplantions.

Methods: RNA interference (RNAi) is an effective approach to degrade RNA levels of a target gene. We used RNAi to reduce CD40 levels in mouse bone marrow-derived DCs. Allogeneic T-lymphocyte proliferation stimulated by DCs was assessed in mixed lymphocyte reactions. A mouse model of heterotopic abdominal heart transplantation was performed to evaluate survival times and histologic grade of acute rejection at 7 days after transplantation. CD4(+)CD25(+) regulatory T cells (Tregs) in peripheral blood were quantified by flow cytometry.

Results: Mouse DCs with reduced CD40 expression lowered the proliferation of recipient T cells. More DCs with silenced CD40 delayed cardiac allograft rejection.

Conclusions: Reduction of CD40 in DCs induced peripheral Tregs and delayed cardiac allograft rejection.