Hänninen A, Salmi M, Simell O, Jalkanen S
Department of Pediatrics and Medical Microbiology, University of Turku, Finland.
Diabetes. 1993 Nov;42(11):1656-62. doi: 10.2337/diab.42.11.1656.
In IDDM, mononuclear cells accumulate in the islets of Langerhans and destroy insulin-producing beta-cells. To study the mechanisms that control extravasation of circulating mononuclear cells into the pancreas, we examined the phenotype of vascular endothelium of the pancreas, propagated a T-cell line from pancreatic islets at the onset of the disease and compared endothelial binding of this cell line in vitro to vascular endothelium in different body regions. The adhesion molecules expressed on the resulting T-cell line and the functional binding capacity of these cells to the endothelium of the normal and diabetic pancreas, mucosa-associated lymphatic tissues, and regional and peripheral lymph nodes were studied. We present evidence of pancreatic endothelial activation in diabetes, leading to endothelial morphology typical for HEVs and accompanying local increase in extravasation of mononuclear cells into the pancreas. Endothelial-cell binding experiments with the T-cell line showed strong adherence of the cells to the endothelium of diabetic pancreas and mucosal lymphoid tissue. The cell line was uniformly CD4-positive, TCR V beta 5.1-positive, LFA-1-positive (CD 11a/CD18), VLA-4 alpha-positive (CD 49d), and CD 44-positive but negative for L-selectin (peripheral lymph node homing receptor). The pancreatic or control cell lines showed no binding to vessels of normal pancreas, and the binding of the pancreatic cell line to the endothelium of peripheral lymph node was weak. Our results suggest that lymphocyte-endothelial cell interactions are important for the accumulation of inflammatory mononuclear cells into the pancreas and imply that lymphocytes derived from the mucosal lymphoid tissue may be involved in the pathogenesis of IDDM.
在胰岛素依赖型糖尿病（IDDM）中，单核细胞在胰岛中积聚并破坏产生胰岛素的β细胞。为了研究控制循环单核细胞渗入胰腺的机制，我们检测了胰腺血管内皮的表型，在疾病发作时从胰岛中培养了一种T细胞系，并在体外比较了该细胞系与不同身体部位血管内皮的结合情况。研究了所得T细胞系上表达的黏附分子以及这些细胞与正常和糖尿病胰腺、黏膜相关淋巴组织以及区域和外周淋巴结内皮的功能结合能力。我们提供了糖尿病中胰腺内皮激活的证据，导致出现高内皮微静脉（HEV）典型的内皮形态，并伴有单核细胞渗入胰腺的局部增加。用T细胞系进行的内皮细胞结合实验表明，细胞与糖尿病胰腺和黏膜淋巴组织的内皮有强烈黏附。该细胞系均为CD4阳性、TCR Vβ5.1阳性、淋巴细胞功能相关抗原-1（LFA-1，CD 11a/CD18）阳性、极迟抗原-4α（VLA-4α，CD 49d）阳性、CD 44阳性，但淋巴细胞归巢受体L-选择素阴性。胰腺或对照细胞系与正常胰腺血管无结合，胰腺细胞系与外周淋巴结内皮的结合较弱。我们的结果表明，淋巴细胞与内皮细胞的相互作用对于炎症单核细胞在胰腺中的积聚很重要，这意味着源自黏膜淋巴组织的淋巴细胞可能参与了IDDM的发病机制。
