Wong S, Guerder S, Visintin I, Reich E P, Swenson K E, Flavell R A, Janeway C A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011.
Diabetes. 1995 Mar;44(3):326-9. doi: 10.2337/diab.44.3.326.
B7-1 is a co-stimulatory molecule that signals T-cells that recognize antigen to proliferate and differentiate into effector T-cells. The same cell must present antigen and express co-stimulatory molecules, such as B7-1, to activate naive T-cells. Thus, tissues that do not express co-stimulatory molecules would not be expected to induce immune responses, while expression of a co-stimulator on tissue cells may convert them into effective antigen-presenting cells and induce autoimmunity. To test this, transgenic mice have been generated that express B7-1 on the beta-cells of the pancreatic islets of Langerhans. On a B6 genetic background, B7-1 expression on beta-cells does not predispose to diabetes. B6 mice are resistant to diabetes. However, when B7-1 is expressed on the beta-cells of B6 mice backcrossed once to the genetically susceptible NOD strain, the onset of diabetes is accelerated and the autoimmune attack intensified. This illustrates that B7-1 is a very potent co-stimulatory molecule in vivo and that its presence on the surface of tissue cells can potentiate the autoimmune process.
B7-1是一种共刺激分子，它向识别抗原的T细胞发出信号，使其增殖并分化为效应T细胞。同一个细胞必须呈递抗原并表达共刺激分子，如B7-1，才能激活初始T细胞。因此，不表达共刺激分子的组织预计不会诱导免疫反应，而组织细胞上共刺激分子的表达可能会将它们转化为有效的抗原呈递细胞并诱导自身免疫。为了验证这一点，已培育出在胰岛β细胞上表达B7-1的转基因小鼠。在B6基因背景下，β细胞上B7-1的表达不会导致糖尿病。B6小鼠对糖尿病具有抗性。然而，当B7-1在与遗传易感性NOD品系回交一次的B6小鼠的β细胞上表达时，糖尿病的发病加速，自身免疫攻击加剧。这表明B7-1在体内是一种非常有效的共刺激分子，其在组织细胞表面的存在可以增强自身免疫过程。
