Type 1 regulatory T (Tr1) cells are an inducible subset of CD4+ Tr cells characterized by high levels of interleukin (IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10-producing Tr1 cell population by transducing human CD4+ T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP LV-IL-10-transduced human CD4+ T (CD4LV-IL-10) cells expressed, upon T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels of IL-4, and markers associated with IL-10. Moreover, CD4LV-IL-10 T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-β dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4LV-IL-10 T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that constitutive over-expression of IL-10 in human CD4+ T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells. © The American Society of Gene & Cell Therapy.

Andolfi, G., Fousteri, G., Rossetti, M., Magnani, C., Jofra, T., Locafaro, G., et al. (2012). Enforced IL-10 expression confers type 1 regulatory T cell (Tr1) phenotype and function to human CD4+ T cells. MOLECULAR THERAPY, 20(9), 1778-1790 [10.1038/mt.2012.71].

Enforced IL-10 expression confers type 1 regulatory T cell (Tr1) phenotype and function to human CD4+ T cells

MAGNANI, CHIARA FRANCESCA;LOCAFARO, GRAZIA;
2012

Abstract

Type 1 regulatory T (Tr1) cells are an inducible subset of CD4+ Tr cells characterized by high levels of interleukin (IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10-producing Tr1 cell population by transducing human CD4+ T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP LV-IL-10-transduced human CD4+ T (CD4LV-IL-10) cells expressed, upon T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels of IL-4, and markers associated with IL-10. Moreover, CD4LV-IL-10 T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-β dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4LV-IL-10 T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that constitutive over-expression of IL-10 in human CD4+ T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells. © The American Society of Gene & Cell Therapy.
Articolo in rivista - Articolo scientifico
Animals; Cell Differentiation; Clonal Anergy; Dendritic Cells; Female; Genes, Reporter; Genetic Vectors; Graft vs Host Disease; Green Fluorescent Proteins; Humans; Interleukin-10; Interleukin-4; Lentivirus; Lymphocyte Activation; Mice; Mice, Nude; T-Lymphocytes, Regulatory; Transduction, Genetic; Gene Expression; Immunomodulation; Molecular Biology; Molecular Medicine; Genetics; Drug Discovery3003 Pharmaceutical Science; Pharmacology
English
2012
20
9
1778
1790
none
Andolfi, G., Fousteri, G., Rossetti, M., Magnani, C., Jofra, T., Locafaro, G., et al. (2012). Enforced IL-10 expression confers type 1 regulatory T cell (Tr1) phenotype and function to human CD4+ T cells. MOLECULAR THERAPY, 20(9), 1778-1790 [10.1038/mt.2012.71].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/122949
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