OBJECTIVE: Indoleamine 2, 3-dioxygenase (IDO) can inhibit rejection of graft via inducing T cell apoptosis. CD40L monoclonal antibody (mAb) inhibits T cell activation. However, the effects of the combination of infusion of dendritic cell (DC) from IDO over-expressed donor mice and CD40L mAb on the treatment of graft rejection after heart transplantation have not been reported.
MATERIALS AND METHODS: Allogeneic heart transplantation mouse model was established. Recipient mice were divided into three groups, including control group, IDO group (in which DC donors received adenoviral vector of IDO) and combined therapy group (which received both IDO over-expressed DC infusion and CD40L mAb injection post transplantation). Survival time and cardiac function were observed, with IDO expression being quantified. Flow cytometry (FCM) was used to analyze T cell apoptosis, while enzyme linked immunosorbent assay (ELISA) was adopted to test the levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-10 (IL-10) and interleukin-6 (IL-6).
RESULTS: IDO expression was significantly elevated in both IDO and combined therapy groups, with enhanced T cell apoptosis compared to control group (p < 0.05). Both groups had better survival time and cardiac functions compared to control group, along with increased IL-10/IL-6 expression and suppressed INF-γ and IL-2 expression (p < 0.05). However, combined therapy had a better efficiency compared to IDO group (p < 0.05).
CONCLUSIONS: Combined therapy of high IDO expressed mouse DC perfusion with CD40L mAb can elongate the survival time of recipient heart and inhibit rejection reaction via facilitating T cell apoptosis. Meanwhile, combined therapy could also regulate the expression of some immune suppressant factors and mediate the Th1/Th2 cytokine balance.Free PDF Download
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To cite this article
Y. Lv, X. Pang, P.-Y. Jia, D.-L. Jia
Combined therapy of infusion of DC from rats with higher expression of IDO and CD40L on rejection post heart transplantation
Eur Rev Med Pharmacol Sci
Vol. 22 - N. 22