Mechanistic insights into achievement of cardiac allograft long-term survival by treatment with immature dendritic cells and sub-dose sirolimus

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Ran TaoShiguang Qian

Abstract

Administration of immature dendritic cells (DC) prolongs but does not result in indefinite allograft survival. We attempted to achieve this goal by adding a sub-therapeutic dose of immunosuppression. DC propagated from B10 (H-2(b)) mouse bone marrow (BM) were transfected with nuclear factor-kappaB (NF-kappaB)-binding-site-specific oligodeoxyribonucleotide (ODN). The allostimulatory activity of transfected and normal DC were examined in mixed-lymphocyte reaction (MLR) and cytotoxic T-lymphocyte (CTL) assays in vitro, and their influence on allograft survival by systemic administration of DC in vivo. Transfection of DC with NF-kappaB ODN resulted in complete abrogation of NF-kappaB activity and inhibition of co-stimulation. Allogeneic (C3H, H-2(k)) T cells stimulated by ODN DC demonstrated impairment in MLR and CTL activity. Administration of ODN DC significantly prolonged B10 allograft survival. In contrast to cyclosporine, which failed to enhance the effect of ODN DC, a combination of ODN DC with sirolimus at 6 mg/kg/day for 6 days achieved long-term survival in all allografts. This was associated with low CTL activity of either graft-infiltrating cells or splenic T cells and increased TUNEL-positive cells in T-cell areas of re...Continue Reading

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Citations

Aug 3, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amandeep BajwaMark D Okusa

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