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Pretreatment of donor dendritic cells with MyD88siRNA to induce tolerance in mouse allograft recipients

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Author:: No author available

Journal Title:: CHINESE JOURNAL OF ORGAN TRANSPLANTATION

Issue:: 8

DOI:: 10.3760/cma.j.issn.0254-1785.2008.08.001

Key Word:: 树突细胞;MyD88;RNA干扰;免疫耐受;Dendritic cells;Myeloid differentiation factor 88;RNA interference;Immune tolerance

Abstract： Objective To explore the effects of donor dendritic cells (DC) treated with MyD88siRNA in tolerance induction in mouse allograft recipients.Methods MyD88siRNA was synthesized chemically and transfected into DC derived from BALB/c bone marrow by RNAi-mate.The DC modified with MyD88siRNA,named MyD88siRNA-DC,were injected into the recipient C57BL/6 mice.The existence of the donor MyD88siRNA-DC in the recipient animal spleens was studied by double-immunofluorescence staining.The responsiveness of the recipient spleen T cells to the donor alloantigen was determined by mixed lymphoeyte reaction(MLR).The cervieal heterotopic heart transplantation model was established with "cuff" technique 7 days after iniection and the cardiac allograft survival time was observed.Pathological analysis was performed and the levels of cytokines in the serum were determined using ELISA. Results The survival rate of the donor-derived MyDB8siRNA-DC in the recipient spleens was higher than that of the donor derived Day8-DC.The donor-derived MyD88siRNA-DC induced alloantigen-specific T-cell hypo-responsiveness.The cardiac allograft survival time in the MyD88siRNA-DC treated group was longer than that in the Day8-DC group and PBS treated group [(24.50±4.42) days vs (13.67±2.25) days and (6.67±1.3) days,(P＜0.01)].Pathological grade of rejection was significantly lower (P＜0.01).In the MyD88siRNA-DC treated group,the levels of IL-12 and IFN-γ in the serum were decreased significantly (P＜0.01),but the levels of IL-4 and IL-10 in the serum increased significantly (P＜0.01).Conclusions The injection of the donor-derived MyD88 siRNA-DC can lcad to donor-specific tolerance in transplant recipients.The polarization of Th2 response and chimerism of recipient may play important roles on immune tolerance to cardiac allografts.

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