PANCREATIC TRANSPLANTATION AND DIABETES MELLITUS

针对胰岛自身抗体的检测 血清中细胞表面抗体(ICSA)和胰岛细胞抗体(ICA) 1型糖尿病患者一直很难标准化。 在这个项目中，我们将检查所选胰岛的独特型 细胞单抗将被证明有助于发展 胰岛细胞自身抗体的标准化放射免疫测定法。孤立 已有研究表明，胰岛对免疫非常脆弱。 拒绝。已经提出了一种假说，即具有2类基因的细胞 MHC抗原负责启动排斥反应过程。自.以来 内分泌细胞不表达这些决定因素，有人提出 胰岛内有非内分泌的客体细胞 同种异体移植排斥反应所需的信号。单克隆抗体 针对犬的2类MHC抗原将被用作 免疫吸附试剂从分散的细胞中删除这些细胞成分 内分泌胰岛细胞制剂。胰腺再加重后 内分泌细胞，在组织培养中，它们将被植入肾下 用比格犬胰腺切除胶囊测定高血糖 在没有免疫抑制治疗的情况下是逆转的。最后，没有什么是 已知胰岛细胞表面的抗原。然而，还有一大批 细胞表面受体，包括毒素受体，如四氧嘧啶和 破伤风毒素；胰岛素促分泌剂受体，如推定的 糖受体；儿茶酚胺受体、胆碱能药物和 胃抑制多肽等胃肠因子；β受体 细胞营养性病毒；以及生长因子受体，仅举一例 很少有，是高度组织的膜结构的组成部分，它将 证明是分化抗原的丰富来源，可能类似于 范围到已经在淋巴细胞膜上识别的那些。 针对大鼠、犬和人类胰岛细胞产生的单抗 将使我们能够开始研究组织和功能 其中一些胰岛细胞质膜蛋白的关系。

The detection of autoantibodies directed against pancreatic islets, islet cell surface antibody (ICSA) and islet cell antibody (ICA), in sera of patients with Type 1 diabetes mellitus has been difficult to standardize. In this project, we will examine whether the idiotype of selected islet cell monoclonal antibodies will prove to be helpful in the development of a standardized radioimmunoassay for islet cell autoantibodies. Isolated pancreatic islets have been shown to be highly vulnerable to immune rejection. The hypothesis has been advanced that cells which bear Class 2 MHC antigens are responsible for initiating the rejection process. Since endocrine cells do not express these determinants, it has been proposed that there are non-endocrine passenger cells within the islet carrying signals that are required for allograft rejection. Monoclonal antibodies directed against canine Class 2 MHC antigens will be used as immunoadorbtion reagents to delete these cellular elements from dispersed endocrine islet cells preparations. Following reaggragation of pancreatic endocrine cells, in tissue culture, they will be implanted under the renal capsule of pancreatectomized beagle dogs to determine whether hyperglycemia is reversed in the absence of immunosuppression therapy. Lastly, little is known about antigens on the surface of islet cells. Yet a vast array of cell surface receptors, including receptors for toxins such as alloxan and tetanus toxin; receptors for insulin secretagogues such as putative glucoreceptors; and receptors for catecholamines, cholinergic agents, and gut factors such as gastric inhibitory polypeptide; receptors for beta cytotrophic viruses; and receptors for growth factors, to mention just a few, are constituents of a highly organized membrane structure that will prove to be a rich source of differentiation antigens, perhaps similar in scope to those already identified on lymphocyte plasma membranes. Monoclonal antibodies, generated against rat, canine, and human islet cells will allow us to begin to study the organizational and functional relationships of some of these islet cell plasma membrane proteins.