Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3 Treg cells

Johan Verhagen, David Wraith

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
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Adoptive transfer of antigen-specific, in vitro-induced Foxp3+ Treg (iTreg) cells protects against autoimmune disease. To generate antigen-specific iTreg cells at high purity, however, remains a challenge. Whereas polyclonal T cell stimulation with anti-CD3 and anti-CD28 antibody yields Foxp3+ iTreg cells at a purity of 90-95%, antigen-induced iTreg cells typically do not exceed a purity of 65-75%, even in a TCR-transgenic model. In a similar vein to thymic Treg cell selection, iTreg cell differentiation is influenced not only by antigen recognition and the availability of TGF-β but also by co-factors including costimulation and adhesion molecules. In this study, we demonstrate that blockade of the T cell integrin Leukocyte Function-associated Antigen-1 (LFA-1) during antigen-mediated iTreg cell differentiation augments Foxp3 induction, leading to approximately 90% purity of Foxp3+ iTreg cells. This increased efficacy not only boosts the yield of Foxp3+ iTreg cells, it also reduces contamination with activated effector T cells, thus improving the safety of adoptive transfer immunotherapy.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalJournal of Immunological Methods
Early online date6 Aug 2014
Publication statusPublished - 1 Dec 2014


  • Adoptive Transfer
  • Animals
  • Autoimmune Diseases
  • Autoimmunity
  • CTLA-4 Antigen
  • Cell Differentiation
  • Cells, Cultured
  • Forkhead Transcription Factors
  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • T-Lymphocytes, Regulatory
  • Transforming Growth Factor beta
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Foxp3
  • LFA-1
  • Treg cell
  • Immunotherapy


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