The delivery of genes that encode immuno-modulatory molecules to the site of the graft, or to the graft itself, has much scope for reducing the harmful local immune response against foreign tissue that occurs in acute and chronic rejection.
Cytokines are soluble mediators of the immune system, and some of them have immunosuppressive effects. The viral form of interleukin 10 (vIL-10) is a protein that is encoded by the Epstein-Barr virus; it is structurally homologous to mouse and human IL-10 but does not possess the T-cell co-stimulatory properties that IL-10 does. Thus, it is a useful tool in gene transfer to tissue where T-cell activation needs to be switched off or downregulated. DeBruyne and colleagues. have demonstrated that gene transfer of vIL-10 to a murine cardiac allograft via vasculature perfusion using DNA-liposome complexes prolonged graft survival (16 days compared with 8 days for untreated grafts). The result was attributed to the vIL-10 gene, because treatment with either an antisense plasmid to vIL-10 or a monoclonal antibody targeted against vIL-10 reversed the graft-prolongation effect. Other cytokine genes, such as transforming growth factor beta (TGF-b), have also been shown to have a significant immunosuppressive effect . This type of approach is not intended to induce immunological tolerance, but might be useful for the delivery of local immunosuppression.
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