title: Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3⁺ Treg cells.
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.
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom. Electronic address: Johan.Verhagen@bristol.ac.uk.
authors.forename: Johan
authors.initials: J
authors.lastname: Verhagen
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Wraith
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016212:Transforming Growth Factor beta
keywords: Autoimmunity; Foxp3; Immunotherapy; LFA-1; Treg cell
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