Vanclée Ariane, Schouten Harry C, Bos Gerard M J
Department of Internal Medicine, Division of Hematology and Oncology, University Hospital Maastricht, The Netherlands.
Transpl Immunol. 2006 Jun;16(1):8-13. doi: 10.1016/j.trim.2006.03.001. Epub 2006 Apr 4.
Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-cell anergy, when antigen presentation occurs in the absence of costimulation as is the case in immature DCs (iDCs). In continuance of publications reporting on the use of iDCs to induce tolerance to various organs, we set out to determine whether tolerance could be induced in a model of allogeneic stem cell transplantation. Immature DCs were obtained by culture with very low concentrations of GM-CSF and by treating DCs with Dexamethasone (Dex). We show that these DCs express low levels of MHCII and costimulatory molecules and that this immature phenotype is retained after application of maturation stimuli. We also prove that these alternatively activated DCs are unable to induce T-cell proliferation in vitro. When used in vivo however, these tolerogenic DCs do not provide tolerance to fully mismatched or haploidentical stem cells.
诱导供体特异性低反应性可减少移植排斥临床环境中强化免疫抑制的需求，而树突状细胞（DCs）可能是实现这一目的的有用工具。除了能够诱导免疫原性T细胞反应外，这些抗原呈递细胞在缺乏共刺激的情况下（如未成熟DCs，即iDCs的情况）进行抗原呈递时，可导致T细胞无反应性。在持续有关于使用iDCs诱导对各种器官耐受性的报道的情况下，我们着手确定在同种异体干细胞移植模型中是否能诱导出耐受性。通过用极低浓度的粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养以及用地塞米松（Dex）处理DCs来获得未成熟DCs。我们发现这些DCs表达低水平的主要组织相容性复合体II类分子（MHCII）和共刺激分子，并且在施加成熟刺激后这种未成熟表型得以保留。我们还证明这些经交替激活的DCs在体外不能诱导T细胞增殖。然而，当在体内使用时，这些耐受性DCs并不能为完全不匹配或单倍体相同的干细胞提供耐受性。
