CD4 T cell differentiation and regulation in autoimmune diabetes

1型糖尿病是一种自身免疫性疾病，免疫系统的细胞攻击胰腺，阻止其产生胰岛素。即使提供新的胰岛素产生细胞作为移植，免疫系统也会简单地摧毁这些细胞。可以使用抑制整个免疫系统的药物，但这些药物有不想要的副作用。成功治疗1型糖尿病的关键是找出哪些细胞导致疾病，以便有选择地针对这些细胞。我们进行了一项筛选，以确定导致糖尿病的免疫细胞在小鼠模型中的特征。这项工作产生了一个惊人的结果；这些细胞很明显是一个特殊的亚群，称为滤泡辅助T细胞。这种免疫细胞亚群可能导致糖尿病的可能性以前还没有被探索过。这项拟议的工作试图调查这些细胞是如何发育的，并确定针对这一亚群的治疗是否可以预防或逆转糖尿病。我们将探索是否可以在1型糖尿病患者的血液样本中检测到滤泡辅助T细胞，并将利用小鼠糖尿病模型来测试靶向这些细胞是否具有有益的效果。

Type 1 diabetes is an autoimmune disease in which cells of the immune system attack the pancreas and prevent it from producing insulin. Even if new insulin-producing cells are provided as a transplant, the immune system simply destroys these too. Medicines are available that suppress the entire immune system, but these have unwanted side effects. The key to successful treatment of type 1 diabetes is to pinpoint which cells cause disease so that these can be selectively targeted. We have performed a screen to characterise the immune cells that cause diabetes in a mouse model. This work has yielded a striking result; the cells are quite clearly a particular subset called follicular helper T cells. The possibility that this subset of immune cells could cause diabetes has not previously been explored. The proposed work seeks to investigate how these cells develop, and determine whether targeting this subset therapeutically can prevent or reverse diabetes. We will explore whether follicular helper T cells can be detected in blood samples from type 1 diabetes patients and will also take advantage of mouse diabetes models so we can test whether targeting these cells has beneficial effects.