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 language | English |
|---|---|
| Pages (from-to) | 194-202 |
| Number of pages | 9 |
| Journal | Molecular Therapy |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2008 |
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ASJC Scopus subject areas
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3
AU - Allan, Sarah E.
AU - Alstad, Alicia N.
AU - Merindol, Natacha
AU - Crellin, Natasha K.
AU - Amendola, Mario
AU - Bacchetta, Rosa
AU - Naldini, Luigi
AU - Roncarolo, Maria Grazia
AU - Soudeyns, Hugo
AU - Levings, Megan K.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
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U2 - 10.1038/sj.mt.6300341
DO - 10.1038/sj.mt.6300341
M3 - Article
VL - 16
SP - 194
EP - 202
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 1
ER -