Weringer E J, Like A A
Department of Pathology, University of Massachusetts Medical School, Worcester 01655.
Am J Pathol. 1988 Aug;132(2):292-303.
The BioBreeding/Worcester (BB/Wor) rat develops a spontaneous disorder that closely resembles human insulin-dependent (Type I) diabetes mellitus. The syndrome is preceded by lymphocytic insulitis that destroys pancreatic beta cells. The morphologic features of the spontaneous insulitis lesions are also observed within islets transplanted beneath the renal capsule of diabetes-prone and diabetic animals. This study reports the results of experiments in which immunohistochemical techniques were used to characterize the phenotype of the infiltrating mononuclear cells and detect the expression of class I and class II MHC antigens in native islets and islet transplants in diabetic and diabetes-prone BB/Wor rats. The infiltrates within native pancreatic islets and islet grafts were comprised predominantly of Ia+ cells (dendritic cells and macrophages) CD4+ cells (helper/inducer lymphocytes and macrophages), CD5+ (pan-T) cells and smaller numbers of CD8+ (cytotoxic/suppressor and NK) cells. Pancreatic and graft insulitis were accompanied by markedly enhanced class I antigen expression on islet and exocrine cells. Class II (Ia) antigens were not detected on normal islet cells, islets undergoing insulitis or on islet transplants subjected to immune attack. In islet grafts stained with polymorphic MAbs that distinguish Ia antigens of donor and host origin, Ia antigen expression was limited to infiltrating dendritic cells and macrophages of host origin. It is concluded that the phenotypes of infiltrating mononuclear cells that comprise the insulitis lesion in spontaneous BB/Wor diabetes, and the inflammatory attack on islets transplanted into diabetic BB/Wor rats are the same, that pancreatic islet and graft insulitis occur in the presence of enhanced class I antigen expression but in the absence of class II antigen expression, and that infiltrating Ia+ cells within islet grafts are exclusively of recipient (BB/Wor) origin and may explain the initiation of immune insulitis within grafts derived from donors of incompatible MHC.
生物繁殖/伍斯特（BB/Wor）大鼠会发生一种自发疾病，与人类胰岛素依赖型（I型）糖尿病极为相似。该综合征之前会出现淋巴细胞性胰岛炎，破坏胰腺β细胞。在易患糖尿病和糖尿病的动物肾被膜下移植的胰岛内，也观察到了自发性胰岛炎病变的形态学特征。本研究报告了实验结果，其中使用免疫组织化学技术来表征浸润单核细胞的表型，并检测糖尿病和易患糖尿病的BB/Wor大鼠的天然胰岛及胰岛移植中I类和II类MHC抗原的表达。天然胰腺胰岛和胰岛移植物中的浸润细胞主要由Ia+细胞（树突状细胞和巨噬细胞）、CD4+细胞（辅助/诱导淋巴细胞和巨噬细胞）、CD5+（泛T）细胞以及少量CD8+（细胞毒性/抑制性和NK）细胞组成。胰腺和移植物胰岛炎伴随着胰岛和外分泌细胞上I类抗原表达的显著增强。在正常胰岛细胞、发生胰岛炎的胰岛或遭受免疫攻击的胰岛移植中未检测到II类（Ia）抗原。在用区分供体和宿主来源Ia抗原的多态性单克隆抗体染色的胰岛移植物中，Ia抗原表达仅限于宿主来源的浸润树突状细胞和巨噬细胞。得出的结论是，构成自发性BB/Wor糖尿病中胰岛炎病变的浸润单核细胞的表型，与对移植到糖尿病BB/Wor大鼠体内的胰岛的炎性攻击相同；胰腺胰岛和移植物胰岛炎在I类抗原表达增强但II类抗原不表达的情况下发生；胰岛移植物内浸润的Ia+细胞完全来自受体（BB/Wor），这可能解释了来自不相容MHC供体的移植物内免疫性胰岛炎的起始。
