Dufour François D, Silveira Pablo A, Baxter Alan G
Comparative Genomics Centre, James Cook University, Townsville, Queensland, Australia.
J Immunotoxicol. 2008 Apr;5(2):249-57. doi: 10.1080/15476910802131543.
Type 1 diabetes is one of the most prevalent autoimmune conditions that develops during childhood and has an increasing incidence worldwide. The disease results from the destruction of pancreatic beta cells mediated by autoreactive T-lymphocytes. In order to develop preventive therapies, the cellular mechanisms responsible for the generation and activation of beta cell-specific T-lymphocytes need to be characterized. Recent studies in the NOD mouse model of autoimmune diabetes suggest that the MHC Class II presentation of beta cell-derived antigens by B-lymphocytes could support the development and activity of autoreactive CD4+ T-lymphocytes in this disease. Interestingly, B-lymphocytes are also the most frequent antigen presenting cells expressing the MHC Class I like molecule, CD1d, the restriction molecule responsible for presentation of lipid and glycolipid antigens to Type 1 NKT cells. Splenic marginal zone B-lymphocytes, which express CD1d at particularly high levels, seem poised to signal to Type 1 NKT cells. In contrast to the disease-promoting role of conventional CD4+ T-lymphocytes, several lines of evidence have shown that Type 1 NKT cells are involved in the prevention of Type 1 Diabetes. This review will analyze current knowledge on the roles of B-lymphocytes and Type 1 NKT cells in the onset of Type 1 Diabetes and explore possible outcomes of their interactions in relation to disease.
1型糖尿病是儿童期最常见的自身免疫性疾病之一，在全球范围内发病率呈上升趋势。该疾病是由自身反应性T淋巴细胞介导的胰腺β细胞破坏所致。为了开发预防性治疗方法，需要明确负责β细胞特异性T淋巴细胞产生和激活的细胞机制。最近在自身免疫性糖尿病的非肥胖糖尿病（NOD）小鼠模型中的研究表明，B淋巴细胞对β细胞衍生抗原的MHC II类呈递可能支持该疾病中自身反应性CD4 + T淋巴细胞的发育和活性。有趣的是，B淋巴细胞也是表达MHC I类样分子CD1d的最常见抗原呈递细胞，CD1d是负责将脂质和糖脂抗原呈递给1型自然杀伤T（NKT）细胞的限制分子。脾边缘区B淋巴细胞，其CD1d表达水平特别高，似乎随时准备向1型NKT细胞发出信号。与传统CD4 + T淋巴细胞促进疾病的作用相反，有几条证据表明1型NKT细胞参与预防1型糖尿病。本综述将分析目前关于B淋巴细胞和1型NKT细胞在1型糖尿病发病中的作用的知识，并探讨它们相互作用与疾病相关的可能结果。
