Paunicka K J, Mellon J, Robertson D, Petroll M, Brown J R, Niederkorn J Y
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX.
Am J Transplant. 2015 Jun;15(6):1490-501. doi: 10.1111/ajt.13240. Epub 2015 Apr 14.
Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a threefold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty, we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft.
尽管未进行HLA配型，但角膜同种异体移植排斥反应的发生率低于10%。然而，二次角膜移植排斥反应的发生率增加了两倍，这并非由于对第一次和第二次移植共有的组织相容性抗原预先致敏，因为角膜移植是随机选择的，未进行组织相容性配型。使用穿透性角膜移植的小鼠模型，我们发现50%的初次角膜移植存活，但随后在对侧眼植入的100%角膜同种异体移植（与第一次移植无关）均发生了排斥反应。手术过程中发生的角膜神经切断导致双眼分泌P物质（SP），这使同种异体移植存活所需的调节性T细胞失活。给予SP拮抗剂可恢复免疫赦免并促进移植物存活。因此，角膜手术会产生一种交感反应，这种反应会永久性地消除后续角膜同种异体移植的免疫赦免，即使是那些植入对侧眼且表达与第一次角膜移植完全不同的一系列外来组织相容性抗原的移植。
