Choi Inho, Kim Sung Dae, Cho Bumrae, Kim Donghee, Park Dongkyoo, Koh Hyun Sook, Kim Bo-Yoon, Kim Jae Young, Yang Jaeseok, Ahn Curie
Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Mol Immunol. 2008 Jan;45(2):575-80. doi: 10.1016/j.molimm.2007.06.161. Epub 2007 Aug 1.
Xenotransplantation is a promising alternative to overcome donor shortage in transplantation. CD40 molecule plays an important role in the interaction of T cells with antigen-presenting cells and in the activation of vascular endothelial cells. We investigated whether the xenogeneic interaction between human CD40L (hCD40L) on T cells and porcine endothelial CD40 (pCD40) can activate porcine endothelial cells (PECs). The interaction between hCD40L and pCD40 induced the expression of chemokines on PECs as well as MHC and adhesion molecules. Furthermore, NF-kappaB signaling was activated in HEK 293 cells expressing pCD40 and PECs by stimulation with hCD40L+ Jurkat T clones. Both anti-CD40L neutralizing antibodies and NF-kappaB signal inhibitors interfered with immune activation of PECs. Overall, this study shows that xenogeneic interaction between hCD40L and pCD40 can activate PECs through NF-kappaB signaling, and therefore may contribute to acute vascular rejection in xenotransplantation.
异种移植是克服移植供体短缺的一种有前景的替代方法。CD40分子在T细胞与抗原呈递细胞的相互作用以及血管内皮细胞的激活中起重要作用。我们研究了T细胞上的人CD40L（hCD40L）与猪内皮CD40（pCD40）之间的异种相互作用是否能激活猪内皮细胞（PEC）。hCD40L与pCD40之间的相互作用诱导了PEC上趋化因子以及MHC和黏附分子的表达。此外，通过用hCD40L + Jurkat T克隆刺激，在表达pCD40的HEK 293细胞和PEC中激活了NF-κB信号传导。抗CD40L中和抗体和NF-κB信号抑制剂均干扰了PEC的免疫激活。总体而言，本研究表明hCD40L与pCD40之间的异种相互作用可通过NF-κB信号传导激活PEC，因此可能导致异种移植中的急性血管排斥反应。
