Emmer Peter M, van der Vlag Johan, Adema Gosse J, Hilbrands Luuk B
Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, the Netherlands.
Transplantation. 2006 May 27;81(10):1451-9. doi: 10.1097/01.tp.0000208801.51222.bd.
Immature dendritic cells (imDC) can prolong allograft survival in murine transplantation models. Recent data indicate that semi-mature or alternatively activated DC (aaDC) may be even more tolerogenic.
We compared the phenotype and regulatory capacity of: a) imDC, cultured in the presence of dexamethasone (DEX), b) mature DC (matDC), activated with LPS, and c) aaDC, activated with LPS after pretreatment with DEX.
As compared to imDC, aaDCs displayed a slight upregulation of CD40 while expression levels of MHC-II and CD86 remained low. The production of proinflammatory cytokines, in particular IL-12, by aaDC was much lower than by matDC while both produced similar amounts of the regulatory cytokine IL-10 leading to an increased IL-10/IL-12 ratio for aaDC. After infusion of donor type aaDCs, responder cells isolated from the recipient mice showed donor-specific hyporesponsiveness to restimulation by matDC. Infusion of matDC was immunogenic, while imDC induced partial hyporesponsiveness. Importantly, pretreatment with donor type aaDC (but not imDC) resulted in prolonged survival of a completely MHC-mismatched heart allograft.
Alternatively activated DC are more efficacious than the classical imDC in the regulation of the alloimmune response, which may be related to a distinct cytokine profile characterized by an increased IL-10/IL12 ratio.
在小鼠移植模型中，未成熟树突状细胞（imDC）可延长同种异体移植物的存活时间。近期数据表明，半成熟或替代性活化树突状细胞（aaDC）可能具有更强的耐受性。
我们比较了以下细胞的表型和调节能力：a）在存在地塞米松（DEX）的情况下培养的imDC，b）用脂多糖（LPS）激活的成熟树突状细胞（matDC），以及c）在用DEX预处理后用LPS激活的aaDC。
与imDC相比，aaDC的CD40表达略有上调，而MHC-II和CD86的表达水平仍然较低。aaDC产生的促炎细胞因子，特别是IL-12，远低于matDC，而两者产生的调节性细胞因子IL-10量相似，导致aaDC的IL-10/IL-12比值增加。输注供体型aaDC后，从受体小鼠分离的应答细胞对matDC的再刺激表现出供体特异性低反应性。输注matDC具有免疫原性，而imDC诱导部分低反应性。重要的是，用供体型aaDC（而非imDC）预处理可延长完全MHC不匹配心脏同种异体移植物的存活时间。
替代性活化树突状细胞在调节同种异体免疫反应方面比经典的imDC更有效，这可能与以增加的IL-10/IL12比值为特征的独特细胞因子谱有关。
