In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes

作者：Qizhi Tang, Kammi Henriksen, Mingying Bi, Erik B. Finger, Gregory L. Szot, Jianqin Ye, Emma L. Masteller, Hugh O. McDevitt, Mark L. Bonyhadi, Jeffrey A. Bluestone · 发表于：The Journal of Experimental Medicine · 年份：2004 · DOI：10.1084/jem.20040139 · 被引用次数：1226 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Diabetes and associated disorders

The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ Tregs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded Tregs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.