Abstract: The invention relates to the field of cell therapy and to an in vitro method for generating T-cell progenitors, comprising the step of exposing CD34+ cells in a medium containing a Notch ligand, a soluble domain of the Delta-like ligand 4, joined to an Fc region of a protein IgG, in the presence of a fragment of fibronectin comprising the motifs RGDS and CS-1 and a heparin-binding domain.

Abstract: Some rare and very severe autoimmune conditions are of hereditary origin such as APECED and IPEX syndrome due to altered negative selection of autoreactive T cells in the thymus or absence of regulatory T cells (Treg). Innovative strategies based on the use of regulatory T cells have been developed. The inventors have now compared 7 different experimental protocols to identify the one allowing to get the most efficacy of Treg to treat Scurfy autoimmune syndrome, a severe autoimmune model mimicking IPEX syndrome. The optimized protocol comprised a preconditioning step using cyclophosphamide and a post-conditioning step using IL-2. Thus, to present invention relates to a method for the treatment of autoimmunity in patient in need thereof comprising the steps of i) administering the patient with an amount of cyclophosphamide, ii) then engrafting the patient with an amount of the population of Treg cells, and iii) finally administering the patient with an amount of IL-2.

Abstract: IPEX (Immune dysregulation Polyendocinopathy X linked) syndrome is a primary immunodeficience caused by mutations in the gene encoding the transcription factor forkhead box P3 (FOXP3), which leads to the loss of function of thymus-derived CD4+CD25+ regulatory T (tTreg) cells. Preclinical and clinical studies suggest that T cell gene therapy approaches designed to selectively restore the repertoire of Treg cells by transfer of wild type FOXP3 gene is a promising potential cure for IPEX. However, there is still a need for a vector that can be used efficiently for the preparation of said Treg cells. The inventors thus compared 6 different lentiviral constructs according to 4 criteria (vector titers, level of transduction of human CD4+ T cells, level of expression of FOXP3 and ?LNGFR genes, degree of correlation between both expression) and selected one construct comprising a bidirectional EFS-PGK promoter that showed remarkable efficiency.

Abstract: IPEX (Immune dysregulation Polyendocrinopathy X linked) syndrome is a primary immunodeficiency caused by mutations in the gene encoding the transcription factor forkhead box P3 (FOXP3), which leads to the loss of function of thymus-derived CD4+CD25+ regulatory T (tTreg) cells. Preclinical and clinical studies suggest that T cell gene therapy approaches designed to selectively restore the repertoire of Treg cells by transfer of wild type FOXP3 gene is a promising potential cure for IPEX. However, there is still a need for a vector that can be used efficiently for the preparation of said Treg cells. The inventors thus compared 6 different lentiviral constructs according to 4 criteria (vector titers, level of transduction of human CD4+ T cells, level of expression of FOXP3 and ?LNGFR genes, degree of correlation between both expression) and selected one construct comprising a bidirectional PGK-EF1a promoter that showed remarkable efficiency.