THE PATHOGENESIS OF ADOPTIVE MURINE AUTOIMMUNE DIABETES REQUIRES AN INTERACTION BETWEEN ALPHA-4-INTEGRINS AND VASCULAR CELL-ADHESION MOLECULE-1
THE PATHOGENESIS OF ADOPTIVE MURINE AUTOIMMUNE DIABETES REQUIRES AN INTERACTION BETWEEN ALPHA-4-INTEGRINS AND VASCULAR CELL-ADHESION MOLECULE-1
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DOI：
10.1172/jci117153
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发表时间：
1994-04-01
影响因子：
15.9
通讯作者：
JANEWAY, CA
中科院分区：
文献类型：
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作者：
BARON, JL;REICH, EP;JANEWAY, CA
采用非肥胖糖尿病小鼠胰岛素依赖型糖尿病（IDDM）过继转移模型，研究α - 4整合素、血管细胞粘附分子1 （VCAM-1）在胰岛素依赖型糖尿病（IDDM）中的作用；细胞间粘附分子1 （ICAM-1）在自身免疫性糖尿病发病机制中的作用。在过继性转移研究中，针对α 4-整合素及其配体之一VCAM-1的特异性抗体能够延缓糖尿病的发病并降低疾病的发病率。这种疾病的阻断伴随着朗格汉斯胰岛淋巴细胞浸润的显著减少。此外，这些抗体优先阻止CD4 T细胞进入组织。ICAM-1特异性抗体对IDDM的发病或发病率影响不大。因此，我们得出结论，α 4-整合素- vcam -1相互作用在T细胞进入朗格汉斯胰岛和IDDM的发病机制中很重要。此外，导致T细胞通过内皮转运的级联事件对于CD4和CD8细胞可能是不同的，并且可能取决于所涉及的内皮。我们的研究结果支持了一个更普遍的结论，即α 4-整合素- vcam -1相互作用可能对激活的效应CD4 T细胞离开血液进入组织清除感染至关重要。
An adoptive transfer model of insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic mouse was used to examine the roles of alpha 4-integrin, vascular cell adhesion molecule 1 (VCAM-1); and intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of autoimmune diabetes. Antibodies specific for both alpha 4-integrin and one of its ligands, VCAM-1, were able to delay onset of diabetes and decrease the incidence of the disease in adoptive transfer studies. This blocking of disease was accompanied by a marked decrease in lymphocytic infiltration of the islets of Langerhans. Furthermore, these antibodies preferentially block entrance of CD4 T cells into the tissue. Antibodies specific for ICAM-1 had little effect on the onset or incidence of IDDM. Thus, we conclude that an alpha 4-integrin-VCAM-1 interaction is important in T cell entry into the islets of Langerhans and in the pathogenesis of IDDM. In addition, the cascade of events leading to T cell transit across endothelium may be different for CD4 and CD8 cells, and may differ depending on the endothelium involved. Our results support the more general conclusion that an alpha 4-integrin-VCAM-1 interaction may be crucial in allowing activated effector CD4 T cells to leave the blood and enter tissue to clear infection.