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.
|Citazione:||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.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Enforced IL-10 expression confers type 1 regulatory T cell (Tr1) phenotype and function to human CD4+ T cells|
|Autori:||Andolfi, G; Fousteri, G; Rossetti, M; Magnani, C; Jofra, T; Locafaro, G; Bondanza, A; Gregori, S; Roncarolo, M|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/mt.2012.71|
|Appare nelle tipologie:||01 - Articolo su rivista|