Prolongation of the survival of rats renal allografts by using tolerogenic dendritic cells treated with curcumin / 中华器官移植杂志

ABSTRACT

Objective To study the efficacy of hypo responsiveness of allogenic T cells induced by curcumin (Cur)-treated dendritic cells (DCs) and influence on survival time of renal allografts in rats.Methods DCs were generated from Wistar rat bone marrow and treated with Cur. The costimulatory molecules (CDl1c, CD80, CD86 and major histocompability complex Ⅱ ) were determined by using flow cytometry,and the production of IL-12 in DCs culture supernatant was examined by using ELISA.The probability of Cur treated DCs to stimulate the proliferation of Lewis rat T cells was detected by using mixed leukocyte reaction (MLR),and the antigen specific T cell hypo responsiveness was analyzed by using secondary MLR. Allograft renal transplantation animal models were established by using Wistar rats as donors,and Lewis rats as recipients.At 7th day before allograft renal transplantation,Cur-treated DCs from donors were injected into recipients through tail vein, meanwhile the non-treated control group and immature DCs control group (immature DCs from donors were injected into recipients through tail vein) were set up.The allograft survival time and allograft pathology after transplantation were assayed.Reaction of T cells from the recipients to mature DCs of donors was analyzed at 14th day.Results Cur restrained the expression of DCs phcnotypc and production of IL-12 (P＜0.05). Cur treated DCs displayed poor ability to stimulate T cells proliferation,and potential to induce antigen specific T cell hypo-responsiveness.The survival time of the renal allograft in Cur-treatcd CDs group [(31.5 ± 6.9) days] was significantly longer (P＜0.05) than in control group [(8.6± 2.1) days] and immature DCs control group [(22.4± 7.4) days],and the pathological lesions in the renal allografts in Cur treated CDs group were milder than in the control group and immature DCs control group.T cells from the recipients injected with Cur-treated DCs showed significant hypo-responsiveness to mature DCs from donors (P＜0.05),but higher proliferation ability to the stimulation of third party independent antigen.Conclusion Cur can suppress the maturation and function of DCs,and induce immune suppression of allogeneic T cells,while infusion of Cur-treated immature DCs can prolong the survival of renal allograft remarkably.