Induction of tolerance in type 1 diabetes via both CD4+ CD25+ T regulatory cells and T regulatory type 1 cells
Induction of tolerance in type 1 diabetes via both CD4+ CD25+ T regulatory cells and T regulatory type 1 cells
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DOI：
10.2337/db05-1576
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发表时间：
2006-06-01
期刊：
影响因子：
7.7
通讯作者：
Roncarolo, Maria-Grazia
中科院分区：
文献类型：
--
作者：
Battaglia, Manuela;Stabilini, Angela;Roncarolo, Maria-Grazia
成功开发新的治疗方法，重新启动自身免疫性自身耐受依赖于T调节（Tr）细胞的诱导。在这里，我们报告说，雷帕霉素与白细胞介素（IL）-10联合有效地阻止I型糖尿病的发展，并诱导长期免疫耐受的非肥胖糖尿病（NOD）小鼠在没有慢性免疫抑制。雷帕霉素介导抑制性CD 4（+）CD 25（+）FoxP 3（+）Tr细胞在胰腺中的积累，从而预防糖尿病。IL-10诱导Tr 1型（Tr 1）细胞，其驻留在脾脏中并防止致糖尿病T细胞迁移到引流淋巴结。这两个Tr细胞亚群共同作用，控制长期耐受小鼠中仍然存在的致糖尿病T细胞。雷帕霉素加IL-10治疗，促进不同的Tr细胞亚群，可能构成一种新的和有效的免疫介导的疾病的耐受诱导方案。
Success in developing novel therapies to recommence self-tolerance in autoimmunity depends on the induction of T regulatory (Tr) cells. Here, we report that rapamycin combined with interleukin (IL)-10 efficiently blocks type I diabetes development and induces long-term immunotolerance in the absence of chronic immunosuppression in nonobese diabetic (NOD) mice. Rapamycin mediates accumulation in the pancreas of suppressive CD4(+)CD25(+) FoxP3(+) Tr cells, which prevent diabetes. IL-10 induces Tr type 1 (Tr1) cells, which reside in the spleen and prevent migration of diabetogenic T-cells to the draining lymph nodes. These two Tr cell subsets act in concert to control diabetogenic T-cells that are still present in long-term tolerant mice. Rapamycin plus IL-10 treatment, promoting distinct subsets of Tr cells, may constitute a novel and potent tolerance-inducing protocol for immune-mediated diseases.