1型糖尿病是由T细胞介导的高度选择性自身免疫性糖尿病。其发生发展是由遗传因素及环境因素共同决定的。糖尿病高危人群向1型糖尿病（T1DM）的发展与调节性T细胞（Treg）维持免疫耐受能力的进行性下降有关。一些报道证明调节性T细胞在针对胰岛自身抗原的外周免疫耐受中起重要作用。最近的证据表明，这种免疫耐受能力的缺陷是由于维持调节性T细胞功能的抗原提呈细胞（APCs）的减少导致的，而不是T细胞自身缺陷所导致的。正因如此，旨在纠正调节性T细胞功能障碍的疗法成为研究热点。
近年来报道证明，在1型糖尿病患者及NOD小鼠中，柯萨奇病毒都被认为是其发生1型糖尿病的共同因素。此前的实验证明NOD小鼠感染柯萨奇病毒4（CB4）后，抗原提呈细胞在感染的β细胞聚集，引起T细胞识别并对β细胞产生自身免疫应答，产生炎症状态，继而引发糖尿病。这表明仅简单的治疗功能下降的Treg细胞是不能够提供长期保护的。本文在1型糖尿病小鼠模型中证明了调整CD11b+CD11c- APCs的炎症状态有助于保护性调节性T细胞（TREG）的上调，使免疫调节能力增加。我们进一步证明，共刺激分子CD40表达的降低在此增加的免疫调节能力中也起到了作用。值得注意的是，Treg细胞的上调完全来自于天然调节性T细胞的增加而不是外周T细胞的转化。这就表明， CD11b+CD11c- APCs炎症状态的调节有助于产生天然调节性T细胞的应答，与适应性Treg细胞应答不同的是其能对更多的抗原产生免疫耐受。因此，1型糖尿病与CDb11+CD11c-APCs激活自身免疫应答能力的下降及免疫调节能力的增加有关，对抗原提呈细胞亚群进行调节是一种重建外周免疫耐受的手段，并可能为预防1型糖尿病等自身免疫性疾病的治疗手段。

Immunomodulation of antigen presenting cells promotes natural regulatory T cells that prevent autoimmune diabetes in NOD mice.
 Progression towards type 1 diabetes (T1D) in susceptible patients is linked to a progressive decline in the capacity of regulatory T cells (Treg) to maintain tolerance. As such, therapies aimed at redressing the failing Treg compartment have been the subject of intense investigation. Treg dysfunction in T1D has recently been linked to a reduced capacity of antigen presenting cells (APCs) to maintain Treg function rather than Treg intrinsic defects. This suggests that therapies aimed simply at addressing the failing Treg compartment are unlikely to provide long-term protection. Here, we demonstrate that modulation of the inflammatory status of CD11b+CD11c- APCs favors the upregulation of protective Tregs in a mouse model of T1D. We further demonstrate that reduced expression of the costimulatory molecule CD40 plays a role in this increased immunoregulatory capacity. Strikingly, Treg upregulation resulted exclusively from an increase in natural Tregs rather than the peripheral conversion of conventional T cells. This suggests that modulation of CD11b+ CD11c- APCs inflammatory properties favors the establishment of natural Treg responses that, unlike adaptive Treg responses, are likely to maintain tolerance to a broad range of antigens. As such, modulation of this APC subset represents a potential therapeutic avenue to reestablish peripheral tolerance and protect from autoimmune diseases such as T1D.

链接： http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22355341/?tool=pubmed