دورية
A combination of cyclophosphamide, interleukin-2 allow CD4+T cells converted to Tregs to control scurfysyndrome
| العنوان: | A combination of cyclophosphamide, interleukin-2 allow CD4+T cells converted to Tregs to control scurfysyndrome |
|---|---|
| المؤلفون: | Delville, Marianne, Bellier, Florence, Leon, Juliette, Klifa, Roman, Lizot, Sabrina, Vinçon, Hélène, Sobrino, Steicy, Thouennon, Romane, Marchal, Armance, Guarrigue, Alexandrine, Olivré, Juliette, Charbonnier, Soëli, Lagresle-Peyrou, Chantal, Lamarthée, Baptiste, Benoist, Christophe, Zuber, Julien, André, Isabelle, Cavazzana, Marina, Six, Emmanuelle, Amendola, Mario, Schambach, Axel, Gross, David |
| المصدر: | Blood; 20210101, Issue: Preprints |
| مستخلص: | Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome is caused by mutations in FOXP3, which lead to the loss of function of regulatory T cells (Treg) and the development of autoimmune manifestations early in life. The selective induction of a Treg program in autologous CD4+T cells by FOXP3gene transfer is a promising approach for curing IPEX. We have established a novel in vivoassay of Treg functionality, based on adoptive transfer of these cells into scurfymice (an animal model of IPEX) and a combination of cyclophosphamide conditioning and interleukin-2 treatment. This model highlighted the possibility of rescuing scurfydisease after the latter’s onset. By using this in vivomodel and an optimized lentiviral vector expressing human Foxp3 and as a reporter a truncated form of the 5 low-affinity nerve growth factor receptor (ΔLNGFR), we demonstrated that the adoptive transfer of FOXP3-transduced scurfyCD4+T cells enabled the long-term rescue of scurfyautoimmune disease. The efficiency was similar to that seen with wild-type Treg. After in vivoexpansion, the converted CD4FOXP3cells recapitulated the transcriptomic core signature for Treg. These findings demonstrate that FOXP3 expression converts CD4+T cells into functional Treg capable of controlling severe autoimmune disease. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00064971 15280020 |
|---|---|
| DOI: | 10.1182/blood.2020009187 |