In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes

Qizhi Tang, Kammi J. Henriksen, Mingying Bi, Erik B. Finger, Greg Szot, Jianqin Ye, Emma L. Masteller, Hugh McDevitt, Mark Bonyhadi, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

850 Scopus citations

Abstract

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+ T regs 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 T regs 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.

Original languageEnglish (US)
Pages (from-to)1455-1465
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number11
DOIs
StatePublished - Jun 7 2004

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Keywords

  • Autoimnmnity
  • CD4CD25 T cells
  • Immunoregulation
  • NOD mice
  • Tolerance

Cite this

Tang, Q., Henriksen, K. J., Bi, M., Finger, E. B., Szot, G., Ye, J., Masteller, E. L., McDevitt, H., Bonyhadi, M., & Bluestone, J. A. (2004). In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. Journal of Experimental Medicine, 199(11), 1455-1465. https://doi.org/10.1084/jem.20040139