Université Paris Descartes, INSERM U1013, Hôpital Necker Enfants Malades, 161 Rue de Sèvres, Paris 75015, France.
Nat Rev Endocrinol. 2010 Mar;6(3):149-57. doi: 10.1038/nrendo.2009.275.
Type 1 diabetes mellitus (T1DM) is a prototypic organ-specific autoimmune disease that results from selective destruction of insulin-secreting beta-cells by immune-mediated inflammation (insulitis), that is, the infiltration of pancreatic islets by autoreactive CD4(+) and CD8(+) T lymphocytes. Current treatment is substitutive-chronic use of exogenous insulin-which, in spite of considerable advances, is still associated with constraints and lack of effectiveness over the long-term in relation to the prevention of vascular and neurological complications. Finding a cure for T1DM is an important medical health challenge, as the disease's incidence is steadily increasing in industrialized countries and projections of future prevalence are alarming. Crucially, as T1DM mainly affects children and young adults, any candidate immune therapy must be safe and avoid chronic use of immunosuppressants that promote sustained depression of immune responses. The ideal approach would, therefore, involve induction or, in the case of established T1DM, restoration of immune tolerance to target autoantigens. This Review presents, in particular, two strategies that are still in clinical development but hold great promise. These strategies are focused on the use of candidate autoantigens and anti-CD3 monoclonal antibodies.
1 型糖尿病（T1DM）是一种典型的器官特异性自身免疫性疾病，由免疫介导的炎症（胰岛炎）导致胰岛素分泌β细胞选择性破坏，即自身反应性 CD4(+)和 CD8(+)T 淋巴细胞浸润胰岛。目前的治疗方法是替代-慢性使用外源性胰岛素-尽管取得了相当大的进展，但在预防血管和神经并发症方面，长期来看仍存在局限性和效果不佳的问题。找到治疗 T1DM 的方法是一个重要的医学健康挑战，因为这种疾病在工业化国家的发病率正在稳步上升，未来的患病率预测令人担忧。至关重要的是，由于 T1DM 主要影响儿童和年轻人，任何候选免疫疗法都必须是安全的，并且避免长期使用免疫抑制剂，以免持续抑制免疫反应。因此，理想的方法将涉及诱导或在已确诊的 T1DM 中恢复对靶自身抗原的免疫耐受。本综述特别介绍了两种仍处于临床开发阶段但前景广阔的策略。这些策略侧重于使用候选自身抗原和抗 CD3 单克隆抗体。
