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

Johan Verhagen*, David C. Wraith

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)

Abstract

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
Volume414
Early online date6 Aug 2014
DOIs
Publication statusPublished - 1 Dec 2014

Bibliographical note

Copyright © 2014. Published by Elsevier B.V.

Keywords

  • Autoimmunity
  • Foxp3
  • Immunotherapy
  • LFA-1
  • Treg cell

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