Herold K G, Lenschow D J, Bluestone J A
Department of Medicine, University of Illinois at Chicago 60612, USA.
Immunol Res. 1997 Feb;16(1):71-84. doi: 10.1007/BF02786324.
The initiation and progression of autoimmune diseases, such as insulin-dependent diabetes mellitus (IDDM), are complex processes that depend on autoantigen exposure, genetic susceptibility, and secondary events that promote autoaggression. T-cell costimulation, largely mediated by CD28/B7 interactions, is a major regulatory pathway in the activation and differentiation of T-cells that cause IDDM in murine models. In this article, we summarize our results in two models of IDDM: the nonobese diabetic (NOD) mouse and diabetes induced with multiple low doses of streptozotocin (MDSDM). In both of these models, blockade of CD28/B7 costimulation regulates the development of disease. The effects of blockade vary with the intensity of cognate signal delivered to the T-cells, the timing of the costimulatory signal, and perhaps even the CD28 ligand expressed on antigen-presenting cells (APCs). Our results suggest that targeting CD28/B7 signals is a feasible approach for treatment and prevention of recurrence of autoimmune diabetes. However, the dynamic nature of these interactions highlights the importance of a clear understanding of their role in regulation of the disease.
自身免疫性疾病（如胰岛素依赖型糖尿病，IDDM）的起始和进展是复杂的过程，这取决于自身抗原暴露、遗传易感性以及促进自身攻击的继发事件。T细胞共刺激主要由CD28/B7相互作用介导，是在小鼠模型中导致IDDM的T细胞活化和分化的主要调节途径。在本文中，我们总结了在两种IDDM模型中的研究结果：非肥胖糖尿病（NOD）小鼠和多次低剂量链脲佐菌素诱导的糖尿病（MDSDM）。在这两种模型中，阻断CD28/B7共刺激可调节疾病的发展。阻断的效果因传递给T细胞的同源信号强度、共刺激信号的时机，甚至可能因抗原呈递细胞（APC）上表达的CD28配体而异。我们的结果表明，靶向CD28/B7信号是治疗和预防自身免疫性糖尿病复发的可行方法。然而，这些相互作用的动态性质凸显了清楚了解它们在疾病调节中的作用的重要性。
