Campos-Acuña Javier, Pérez Francisco, Narváez Edgar, Campos-Mora Mauricio, Gajardo Tania, Catalán Diego, Aguillón Juan C, Pino-Lagos Karina
Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, 3er Piso, Pabellon I, Santiago 8380453, Chile.
Immunotherapy. 2015;7(2):101-10. doi: 10.2217/imt.14.116.
To date, there is no human dendritic cell (DC) based therapy to prevent allograft rejection in transplanted patients. Here, we evaluate a potential protocol using a murine in vivo transplant model.
MATERIALS & METHODS: We generated murine bone marrow-derived DCs (BM-DCs), modulated with rapamycin (Rapa) and activated with monophosphoryl lipid A (Rapamycin-treated and monophosphoryl lipid A-matured DCs [Rapa-mDCs]). DCs phenotype was evaluated by flow cytometry, cytokine production by ELISA and their T-cell stimulatory ability was tested in co-cultures with CD4(+) T cells. Using an in vivo skin graft model, we evaluated DCs tolerogenicity.
In vitro, Rapa-mDCs exhibit a semi-mature phenotype given by intermediate levels of co-stimulatory molecules and cytokines, and inhibit CD4(+) T-cell proliferation. In vivo, skin-grafted mice treated with Rapa-mDCs show high allograft survival, accumulation of Foxp3(+) Tregs and cytokine pattern modification.
Rapa-mDCs re-educate the inflammatory microenvironment, promoting skin-allograft survival.
迄今为止，尚无基于人树突状细胞（DC）的疗法来预防移植患者的同种异体移植物排斥反应。在此，我们使用小鼠体内移植模型评估一种潜在方案。
我们制备了经雷帕霉素（Rapa）调节并用单磷酰脂质A激活的小鼠骨髓来源的DC（雷帕霉素处理且单磷酰脂质A成熟的DC [Rapa-mDCs]）。通过流式细胞术评估DC的表型，通过酶联免疫吸附测定法检测细胞因子的产生，并在与CD4(+) T细胞的共培养中测试其T细胞刺激能力。使用体内皮肤移植模型，我们评估了DC的致耐受性。
在体外，Rapa-mDCs表现出由共刺激分子和细胞因子的中等水平所赋予的半成熟表型，并抑制CD4(+) T细胞增殖。在体内，用Rapa-mDCs处理的皮肤移植小鼠显示出高同种异体移植物存活率、Foxp3(+)调节性T细胞积累和细胞因子模式改变。
Rapa-mDCs重塑炎性微环境，促进皮肤同种异体移植物存活。
