Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors
Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors
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DOI：
10.1111/j.1600-6143.2004.00683.x
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发表时间：
2005-02-01
影响因子：
8.8
通讯作者：
Cuturi, MC
中科院分区：
文献类型：
--
作者：
Pêche, H;Trinité, B;Cuturi, MC
最近的研究表明，特定的树突状细胞（DC）亚群可能是致耐受性的。为了测试不同DC亚群调节同种异体移植排斥反应的能力，我们用低剂量的GM-CSF和IL-4产生了两种不同的大鼠骨髓来源的DC（BMDC）群体。非贴壁群体（nBMDC）是“经典”DC，其能够刺激幼稚同种异体T细胞，并且可以使用各种刺激物诱导完全成熟。相比之下，贴壁细胞群（aBMDC），显示出不成熟的表型，不能刺激T细胞，更耐成熟。我们发现，移植前一天注射同基因aBMDCs，可显著延长心脏移植物存活时间，并降低抗供体体液和细胞反应。类似地，在无移植物的KLH免疫模型中，同基因aBMDC抑制脾脏中但不抑制淋巴结中对KLH的T细胞应答。这种效应不是抗原特异性的，可以用诱导型一氧化氮合酶抑制剂逆转。这种区室化的抑制可以部分地由以下事实来解释：静脉内施用的大多数同源粘附细胞在脾脏中发现，其中一些细胞到达T细胞区域。这些数据表明，同基因aBMDC可以调节免疫应答。
Recent studies suggest that particular dendritic cells (DC) subpopulations may be tolerogenic. To test the capacity of different DC subpopulations to modulate allograft rejection, we generated two distinct populations of rat bone marrow-derived DCs (BMDC) with low doses of GM-CSF and IL-4. The non-adherent population (nBMDC), which are the 'classical' DCs was able to stimulate naive allogeneic T cells and could be induced to completely mature using various stimuli. In contrast, the adherent population (aBMDC), which displayed an immature phenotype, was unable to stimulate T cells and was more resistant to maturation. We found that syngeneic aBMDCs, injected one day before transplantation, induced significant prolongation of heart allograft survival and decreased anti-donor humoral and cellular responses. Similarly, syngeneic aBMDCs inhibited T-cell responses to KLH in the spleen but not in lymph node in a KLH immunization model without graft. This effect was not antigen specific and could be reversed using an inhibitor of inducible nitric oxide synthase. This compartmentalized inhibition could be in part explained by the fact that the majority of syngeneic adherent cells administered intravenously were found in the spleen with some of them reaching the T-cell areas. These data suggest that syngeneic aBMDCs can modulate immune responses.