Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3

Sarah E. Allan, Alicia N. Alstad, Natacha Merindol, Natasha K. Crellin, Mario Amendola, Rosa Bacchetta, Luigi Naldini, Maria Grazia Roncarolo, Hugo Soudeyns, Megan K. Levings

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Abstract

Therapies based on enhancing the numbers and/or function of T regulatory cells (Tregs) represent one of the most promising approaches to restoring tolerance in many immune-mediated diseases. Several groups have investigated whether human Tregs suitable for cellular therapy can be obtained by in vitro expansion, in vitro conversion of conventional T cells into Tregs, or gene transfer of the FOXP3 transcription factor. To date, however, none of these approaches has resulted in a homogeneous and stable population of cells that is as potently suppressive as ex vivo Tregs. We developed a lentivirus-based strategy to ectopically express high levels of FOXP3 that do not fluctuate with the state of T-cell activation. This method consistently results in the development of suppressive cells that are as potent as Tregs and can be propagated as a homogeneous population. Moreover, using this system, both naïve and memory CD4+ T cells can be efficiently converted into Tregs. To date, this is the most efficient and reliable protocol for generating large numbers of suppressive CD4+ Tregs, which can be used for further biological study and developed for antigen-specific cellular therapy applications.

Original languageEnglish
Pages (from-to)194-202
Number of pages9
JournalMolecular Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2008

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ASJC Scopus subject areas

  • Molecular Biology

Cite this

Allan, S. E., Alstad, A. N., Merindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., Naldini, L., Roncarolo, M. G., Soudeyns, H., & Levings, M. K. (2008). Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Molecular Therapy, 16(1), 194-202. https://doi.org/10.1038/sj.mt.6300341