Kreisel Daniel, Krasinskas Alyssa M, Krupnick Alexander S, Gelman Andrew E, Balsara Keki R, Popma Sicco H, Riha Markus, Rosengard Ariella M, Turka Laurence A, Rosengard Bruce R
Department of Surgery, University of Pennsylvania Health System, Philadelphia 19104, USA.
J Immunol. 2004 Sep 1;173(5):3027-34. doi: 10.4049/jimmunol.173.5.3027.
Expression of MHC class II by donor-derived APCs has been shown to be important for allograft rejection. It remains controversial, however, whether nonhemopoietic cells, such as vascular endothelium, possess Ag-presenting capacity to activate alloreactive CD4(+) T lymphocytes. This issue is important in transplantation, because, unlike hemopoietic APCs, allogeneic vascular endothelium remains present for the life of the organ. In this study we report that cytokine-activated vascular endothelial cells are poor APCs for allogeneic CD4(+) T lymphocytes in vitro and in vivo despite surface expression of MHC class II. Our in vitro observations were extended to an in vivo model of allograft rejection. We have separated the allostimulatory capacity of endothelium from that of hemopoietic APCs by using bone marrow chimeras. Hearts that express MHC class II on hemopoietic APCs are acutely rejected in a mean of 7 days regardless of the expression of MHC class II on graft endothelium. Alternatively, hearts that lack MHC class II on hemopoietic APCs are acutely rejected at a significantly delayed tempo regardless of the expression of MHC class II on graft endothelium. Our data suggest that vascular endothelium does not play an important role in CD4(+) direct allorecognition and thus does not contribute to the vigor of acute rejection.
供体来源的抗原呈递细胞（APCs）表达MHC II类分子已被证明对同种异体移植排斥反应很重要。然而，非造血细胞，如血管内皮细胞，是否具有激活同种异体反应性CD4(+) T淋巴细胞的抗原呈递能力仍存在争议。这个问题在移植中很重要，因为与造血APCs不同，同种异体血管内皮细胞在器官的整个生命周期中都存在。在本研究中，我们报告细胞因子激活的血管内皮细胞在体外和体内对同种异体CD4(+) T淋巴细胞而言都是较差的APCs，尽管其表面表达MHC II类分子。我们的体外观察结果扩展到同种异体移植排斥反应的体内模型。我们通过使用骨髓嵌合体将内皮细胞的同种异体刺激能力与造血APCs的同种异体刺激能力区分开来。在造血APCs上表达MHC II类分子的心脏平均在7天内被急性排斥，而与移植内皮细胞上MHC II类分子的表达无关。或者，在造血APCs上缺乏MHC II类分子的心脏被急性排斥的时间明显延迟，而与移植内皮细胞上MHC II类分子的表达无关。我们的数据表明，血管内皮细胞在CD4(+)直接同种异体识别中不发挥重要作用，因此对急性排斥反应的强度没有贡献。
