A combination of cyclophosphamide and interleukin-2 allows CD4 1 T cells converted to Tregs to control scurfy syndrome - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Blood Année : 2021

A combination of cyclophosphamide and interleukin-2 allows CD4 1 T cells converted to Tregs to control scurfy syndrome

Marianne Delville
Florence Bellier
  • Fonction : Auteur
Juliette Leon
  • Fonction : Auteur
Roman Klifa
  • Fonction : Auteur
Sabrina Lizot
  • Fonction : Auteur
Hélène Vinçon
Steicy Sobrino
  • Fonction : Auteur
Romane Thouenon
  • Fonction : Auteur
Armance Marchal
  • Fonction : Auteur
Alexandrine Garrigue
  • Fonction : Auteur
Juliette Olivré
Soëli Charbonnier
Chantal Lagresle-Peyrou
Axel Schambach
  • Fonction : Auteur
Baptiste Lamarthée
Christophe Benoist
  • Fonction : Auteur
Julien Zuber
  • Fonction : Auteur
Marina Cavazzana
Emmanuelle Six

Résumé

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by mutations in forkhead box P3 (FOXP3), which lead to the loss of function of regulatory T cells (Tregs) and the development of autoimmune manifestations early in life. The selective induction of a Treg program in autologous CD4 1 T cells by FOXP3 gene transfer is a promising approach for curing IPEX. We have established a novel in vivo assay of Treg functionality, based on adoptive transfer of these cells into scurfy mice (an animal model of IPEX) and a combination of cyclophosphamide (Cy) conditioning and interleukin-2 (IL-2) treatment. This model highlighted the possibility of rescuing scurfy disease after the latter's onset. By using this in vivo model and an optimized lentiviral vector expressing human Foxp3 and, as a reporter, a truncated form of the low-affinity nerve growth factor receptor (DLNGFR), we demonstrated that the adoptive transfer of FOXP3-transduced scurfy CD4 1 T cells enabled the long-term rescue of scurfy autoimmune disease. The efficiency was similar to that seen with wild-type Tregs. After in vivo expansion, the converted CD4 FOXP3 cells recapitulated the transcriptomic core signature for Tregs. These findings demonstrate that FOXP3 expression converts CD4 1 T cells into functional Tregs capable of controlling severe autoimmune disease. (
Fichier principal
Vignette du fichier
bloodbld2020009187.pdf (1.4 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04416555 , version 1 (25-01-2024)

Identifiants

Citer

Marianne Delville, Florence Bellier, Juliette Leon, Roman Klifa, Sabrina Lizot, et al.. A combination of cyclophosphamide and interleukin-2 allows CD4 1 T cells converted to Tregs to control scurfy syndrome. Blood, 2021, 137 (17), pp.2326-2336. ⟨10.1182/blood.2020009187⟩. ⟨hal-04416555⟩
3 Consultations
1 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More