Campos L, Posselt A M, Deli B C, Mayo G L, Pete K, Barker C F, Naji A
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104.
Transplantation. 1994 Mar 27;57(6):950-3. doi: 10.1097/00007890-199403270-00030.
Freshly isolated allogenic pancreatic islets transplanted into the thymus of transiently immunosuppressed rats are not rejected but survive indefinitely while also inducing a state of specific unresponsiveness that permits survival of secondary donor-strain islets transplanted extrathymically. Since freshly isolated pancreatic islets contain intraislet antigen-presenting cells as well as endocrine cells it is unclear which cellular component is primarily responsible for mediating unresponsiveness. We therefore examined the impact of pretransplant in vitro culture (a maneuver which selectively depletes intraislet APCs) on the capacity of islet allografts to induce unresponsiveness after intrathymic implantation. APC-depleted pancreatic islets, which are known to have reduced immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether or not brief immunosuppression was employed, but failed to promote survival of subsequent donor-strain islets transplanted to an extrathymic site. These findings emphasize the central role of APCs in the induction of transplantation tolerance in this model, and are consistent with the established role of this population in the development of T cell tolerance in the thymus.
将新鲜分离的同种异体胰岛移植到经短暂免疫抑制的大鼠胸腺中，不会被排斥，而是能无限期存活，同时还会诱导一种特异性无反应状态，使二次移植到胸腺外的供体品系胰岛也能存活。由于新鲜分离的胰岛既含有胰岛内抗原呈递细胞（APC），也含有内分泌细胞，因此尚不清楚哪种细胞成分主要负责介导无反应性。因此，我们研究了移植前体外培养（一种能选择性清除胰岛内APC的操作）对胰岛同种异体移植在胸腺内植入后诱导无反应性能力的影响。已知免疫原性降低的APC缺失型胰岛，无论是否采用短暂免疫抑制，都能在同种异体宿主的胸腺中无限期存活，但无法促进随后移植到胸腺外部位的供体品系胰岛的存活。这些发现强调了APC在该模型中诱导移植耐受的核心作用，并且与该细胞群体在胸腺中T细胞耐受形成过程中已确立的作用相一致。
