Roep Bart O
Dept. Immunohaematology and Blood Transfusion, E3-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Diabetologia. 2003 Mar;46(3):305-21. doi: 10.1007/s00125-003-1089-5. Epub 2003 Mar 22.
Type 1 diabetes mellitus results from a T-cell mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The knowledge of the immunopathogenesis has increased enormously in the last two decades. The contribution of T-cells in the pathogenesis is beyond doubt. Therapies directed against T-cells have been shown to halt the disease process and prevent recurrent beta-cell destruction after islet transplantation. Less is known about the nature and function of these T-cells, the cause of the loss of tolerance to islet autoantigens, why the immune system apparently fails to suppress autoreactivity, and whether (or which) autoantigen(s) are critically involved in the initiation or progression of the disease. The contribution of dendritic cells in directing the immune response is clear, while the contribution of B-cells and autoantibodies is subject to reconsideration. Autoreactive T-cells have proven to be valuable tools to study pathogenic or diabetes-related processes. Measuring T-cell autoreactivity has also provided critical information to determine the fate of islet allografts transplanted to Type 1 diabetic patients. Cellular autoimmunity is a difficult study subject, but it has been a worthwhile quest to unravel the role of T-cells in the pathogenesis of Type 1 diabetes. The challenge for the future is to determine which factors contribute to the loss of tolerance to beta-cell antigens, and to define what measures T-cells can provide to suppress autoreactivity, since it is becoming increasingly evident that T-cells provide a two-edged sword: some T-cells could be pathogenic, but others can regulate the disease process and thus form new targets for immunointervention.
1型糖尿病是由遗传易感性个体中T细胞介导的胰腺β细胞自身免疫性破坏所致。在过去二十年中，对免疫发病机制的认识有了极大的提高。T细胞在发病机制中的作用毋庸置疑。针对T细胞的疗法已被证明可以阻止疾病进程，并防止胰岛移植后β细胞的反复破坏。关于这些T细胞的性质和功能、对胰岛自身抗原耐受性丧失的原因、免疫系统为何显然无法抑制自身反应性，以及是否（或哪些）自身抗原在疾病的发生或进展中起关键作用，我们所知较少。树突状细胞在指导免疫反应中的作用是明确的，而B细胞和自身抗体的作用则有待重新审视。自身反应性T细胞已被证明是研究致病或糖尿病相关过程的有价值工具。测量T细胞自身反应性也为确定移植到1型糖尿病患者体内的胰岛同种异体移植物的命运提供了关键信息。细胞自身免疫是一个难以研究的课题，但阐明T细胞在1型糖尿病发病机制中的作用一直是一项有价值的探索。未来的挑战是确定哪些因素导致对β细胞抗原耐受性的丧失，并确定T细胞可以采取哪些措施来抑制自身反应性，因为越来越明显的是，T细胞是一把双刃剑：一些T细胞可能具有致病性，但其他T细胞可以调节疾病进程，从而形成免疫干预的新靶点。
