Damoiseaux J G, Beijleveld L J, van Breda Vriesman P J
Department of Immunology, University of Limburg, Maastricht, The Netherlands.
Clin Exp Immunol. 1994 Jun;96(3):513-20. doi: 10.1111/j.1365-2249.1994.tb06059.x.
Cyclosporin A (CsA) induces a graft-versus-host-like disease (GVHD) in lethally irradiated Lewis rats reconstituted with syngeneic bone marrow. The role of the thymus in the generation of disease has been unequivocally established. It has been suggested that the CsA-induced disappearance of thymic dendritic cells (DC) is responsible for the generation of the autoaggressive cells. In this study we quantify the loss of DC upon in vivo CsA administration in normal and bone marrow-reconstituted rats using an isolation technique. The phenotype of the DC is determined using MoAbs recognizing antigens which are expressed on thymic medullary DC. Furthermore, the functional aspects are assessed by determining the antigen presentation capacity. Short-term CsA exposure clearly affects the number of DC isolated from the thymus in a concentration-dependent manner. However, in all instances a substantial number of DC can be isolated from CsA-treated animals. These isolated DC exhibit an identical phenotype and function as DC isolated from control animals. Therefore, the partial deficiency of DC can not be held as essential for loss of tolerance.
环孢素A（CsA）可在接受同基因骨髓重建的经致死性照射的Lewis大鼠中诱发移植物抗宿主样疾病（GVHD）。胸腺在疾病发生中的作用已得到明确证实。有人提出，CsA诱导的胸腺树突状细胞（DC）消失是自身攻击性细胞产生的原因。在本研究中，我们使用一种分离技术，对正常和骨髓重建大鼠体内给予CsA后DC的损失进行量化。使用识别胸腺髓质DC上表达抗原的单克隆抗体来确定DC的表型。此外，通过测定抗原呈递能力来评估其功能方面。短期CsA暴露明显以浓度依赖的方式影响从胸腺分离的DC数量。然而，在所有情况下，都能从CsA处理的动物中分离出大量DC。这些分离出的DC表现出与从对照动物中分离出的DC相同的表型和功能。因此，DC的部分缺陷不能被认为是耐受性丧失的必要条件。
