Objective:To investigate the impact of IFN-γ on cardiac transplant tolerance induced by blockade of CD40-CD40 ligand costimulation pathway in mice.
Methods:IFN-γ expression in cardiac grafts and spleens from syngeneic and allogeneic recipients with or without treatment of anti-CD40 ligand monoclonal antibody (MR-1) was examined by realtime RT-PCR. The survival time of cardiac grafts in Wild type and IFN-γ-deficient recipients was investigated. Mixed lymphocyte reaction (MLR) of CD4+T cells and cytotoxic T lymphocyte assay of CD8+T cells from Wild type recipients and IFN-γ-deficient recipients administrated with MR-1 were also studied.
Results:Rejected cardiac allogafts showed significantly higher expression of IFN-γ than tolerant allogafts. Cardiac allograft survival was not prolonged in nonimmunosuppressed IFN-γ-deficient mice. In fact, graft survival time in IFN-γ-deficient mice was somewhat shorter than that observed in Wild type recipients. Administration of MR-1 induced long-term cardiac allograft survival in Wild type recipients, but failed to do so in the IFN-γ-deficient group. Our results also provided evidence that in vivo absence of IFN-γ in recipients facilitated the proliferation and CTL generation of T cells.
Conclusions:IFN-γ faciliates the formation of transplant tolerance induced by blockade of CD40-CD40 ligand costimulation pathway.