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

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • BRISTOL UNIVERSITY

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.

Details

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalJournal of Immunological Methods
Volume414
Publication statusPublished - 1 Dec 2014

Keywords

  • 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