Vaarala Outi
Department of Molecular Medicine, National Public Health Institute, Biomedicum, 00251 Helsinki, Finland.
Ann N Y Acad Sci. 2002 Apr;958:39-46. doi: 10.1111/j.1749-6632.2002.tb02945.x.
Accumulating data suggest that the gut immune system plays a role in the development of autoimmune diabetes: (1) Diet modifies the incidence of autoimmune diabetes and the phenotype of the islet-infiltrating T cells in the animal models of human type 1 diabetes; (2) gut-associated homing receptor beta7-integrin is found on the islet-infiltrating T cells in both human type 1 diabetes and in the animal models of autoimmune diabetes; (3) mesenterial lymphocytes from young NOD mice are able to transfer diabetes to healthy recipients; (4) autoantigen feeding modifies the disease development in the animal models (prevents or accelerates autoimmune diabetes). In humans, a link between the gut immune system and type 1 diabetes has also been suggested. Early introduction of cow milk formulas in infancy may increase the risk of type 1 diabetes. We have demonstrated that primary immunization to a beta cell-specific autoantigen, insulin, occurs in the gut by exposure to cow milk formulas, which contain immunogenic bovine insulin. The induced antibody and T cell responses to bovine insulin cross-react with human insulin. In children at genetic risk who developed beta cell autoimmunity, bovine insulin-binding antibodies increased during follow-up in contrast to autoantibody-negative children. This suggests that insulin-specific immune response induced by dietary insulin may not be controlled in children prone to beta cell autoimmunity. The gut immune system has a key role in controlling insulin-specific immunity induced by dietary insulin. Indeed, indications for aberrant function of the gut immune system have been reported in type 1 diabetes, such as intestinal immune activation and increased intestinal permeability. Research on the gut immune system in human type 1 diabetes is needed to reveal the role of oral immunity in this disease.
越来越多的数据表明，肠道免疫系统在自身免疫性糖尿病的发生发展中起作用：（1）饮食可改变人类1型糖尿病动物模型中自身免疫性糖尿病的发病率和胰岛浸润T细胞的表型；（2）在人类1型糖尿病和自身免疫性糖尿病动物模型中，均可在胰岛浸润T细胞上发现肠道相关归巢受体β7整合素；（3）年轻非肥胖糖尿病（NOD）小鼠的肠系膜淋巴细胞能够将糖尿病转移给健康受体；（4）自身抗原喂养可改变动物模型中的疾病发展（预防或加速自身免疫性糖尿病）。在人类中，也有人提出肠道免疫系统与1型糖尿病之间存在联系。婴儿期过早引入牛奶配方奶粉可能会增加患1型糖尿病的风险。我们已经证明，通过接触含有免疫原性牛胰岛素的牛奶配方奶粉，肠道会对β细胞特异性自身抗原胰岛素进行初次免疫。诱导产生的针对牛胰岛素的抗体和T细胞反应会与人类胰岛素发生交叉反应。与自身抗体阴性的儿童相比，有β细胞自身免疫遗传风险的儿童在随访期间牛胰岛素结合抗体增加。这表明，饮食中的胰岛素诱导的胰岛素特异性免疫反应在易患β细胞自身免疫的儿童中可能无法得到控制。肠道免疫系统在控制饮食中胰岛素诱导的胰岛素特异性免疫方面起关键作用。事实上，在1型糖尿病中已经报道了肠道免疫系统功能异常的迹象，如肠道免疫激活和肠道通透性增加。需要对人类1型糖尿病中的肠道免疫系统进行研究，以揭示口服免疫在这种疾病中的作用。
