Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
J Immunol. 2011 Aug 15;187(4):1745-53. doi: 10.4049/jimmunol.1004112. Epub 2011 Jul 11.
The ability to regulate ongoing inflammation using regulatory T cells (Tregs) is under intense investigation. Strategies to induce and expand Ag-specific Tregs are being developed, and whether various types of Tregs are suppressive in the inflammatory conditions associated with ongoing disease needs to be determined. In this study, we report that TGF-β-induced Tregs (iTregs) and expanded Tregs specific for a major self-Ag in autoimmune gastritis suppress inflammation and associated pathology when administered late in the process of ongoing disease. Transferred iTregs localized to the stomach, maintained Foxp3 and suppressor functions, and engaged several distinct mechanisms to alleviate disease progression. In addition to suppressing the production of inflammatory cytokines in the stomach and preventing the destruction of parietal cells, we show that iTregs secrete numerous chemokines and regulate both iTreg and effector T cell trafficking into the stomach. These data support efforts to use iTregs in therapies to treat autoimmunity and inflammatory diseases and provide novel insight into the biological mechanisms of iTreg-mediated immune suppression.
利用调节性 T 细胞（Tregs）来调节持续的炎症反应正受到深入研究。目前正在开发诱导和扩增抗原特异性 Tregs 的策略，并且需要确定各种类型的 Tregs 在与持续疾病相关的炎症情况下是否具有抑制作用。在这项研究中，我们报告称，转化生长因子-β诱导的 Tregs（iTregs）和针对自身免疫性胃炎中主要自身抗原的扩增 Tregs，在持续疾病过程的后期给药时，可抑制炎症和相关病理。转移的 iTregs 定位于胃，保持 Foxp3 和抑制功能，并通过几种不同的机制来减轻疾病进展。除了抑制胃中炎症细胞因子的产生和防止壁细胞的破坏外，我们还表明，iTregs 分泌多种趋化因子，并调节 iTreg 和效应 T 细胞向胃中的迁移。这些数据支持利用 iTregs 治疗自身免疫和炎症性疾病的努力，并为 iTreg 介导的免疫抑制的生物学机制提供了新的见解。
