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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Regulatory T-Lymphocytes
T-Lymphocytes
Lentivirus
Immune System Diseases
Population Dynamics
Transcription Factors
Therapeutics
Antigens
Population
Genes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Allan, S. E., Alstad, A. N., Merindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., ... 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

Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. / Allan, Sarah E.; Alstad, Alicia N.; Merindol, Natacha; Crellin, Natasha K.; Amendola, Mario; Bacchetta, Rosa; Naldini, Luigi; Roncarolo, Maria Grazia; Soudeyns, Hugo; Levings, Megan K.

In: Molecular Therapy, Vol. 16, No. 1, 01.2008, p. 194-202.

Research output: Contribution to journalArticle

Allan, SE, Alstad, AN, Merindol, N, Crellin, NK, Amendola, M, Bacchetta, R, Naldini, L, Roncarolo, MG, Soudeyns, H & Levings, MK 2008, 'Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3', Molecular Therapy, vol. 16, no. 1, pp. 194-202. https://doi.org/10.1038/sj.mt.6300341
Allan, Sarah E. ; Alstad, Alicia N. ; Merindol, Natacha ; Crellin, Natasha K. ; Amendola, Mario ; Bacchetta, Rosa ; Naldini, Luigi ; Roncarolo, Maria Grazia ; Soudeyns, Hugo ; Levings, Megan K. / Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. In: Molecular Therapy. 2008 ; Vol. 16, No. 1. pp. 194-202.
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