In vitro correction of JAK3-deficient severe combined immunodeficiency by retroviral-mediated gene transduction

Détails

ID Serval
serval:BIB_A727DD27C251
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In vitro correction of JAK3-deficient severe combined immunodeficiency by retroviral-mediated gene transduction
Périodique
J Exp Med
Auteur(s)
Candotti F., Oakes S. A., Johnston J. A., Notarangelo L. D., O'Shea J. J., Blaese R. M.
ISSN
0022-1007 (Print)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
1996
Volume
183
Numéro
6
Pages
2687-92
Langue
anglais
Notes
Candotti, F
Oakes, S A
Johnston, J A
Notarangelo, L D
O'Shea, J J
Blaese, R M
eng
A.042/Telethon/Italy
Research Support, Non-U.S. Gov't
J Exp Med. 1996 Jun 1;183(6):2687-92.
Résumé
Mutations affecting the expression of the Janus family kinase JAK3 were recently shown to be responsible for autosomal recessive severe combined immunodeficiency (SCID). JAK3-deficient patients present with a clinical phenotype virtually indistinguishable from boys affected by X-linked SCID, a disease caused by genetic defects of the common gamma chain (gamma c) that is a shared component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. The specific interaction of JAK3 and gamma c represents the biochemical basis for the similarities between these two immunodeficiencies. Both forms of SCID are characterized by recurrent, severe infections leading to death in infancy unless successfully treated by allogeneic bone marrow transplantation. Because of the potentially lethal complications associated with allogeneic bone marrow transplantation and the frequent lack of suitable marrow donors, the development of alternative forms of therapy is highly desirable. To this end, we investigated a retroviral-mediated gene correction approach for JAK3-deficiency. A vector carrying a copy of JAK3 cDNA was constructed and used to transduce B cell lines derived from patients with JAK3-deficient SCID. We demonstrate restoration of JAK3 expression and phosphorylation upon IL-2 and IL-4 stimulation. Furthermore, patients' cells transduced with JAK3 acquired the ability to proliferate normally in response to IL-2. These data indicate that the biological defects of JAK3-deficient cells can be efficiently corrected in vitro by retroviral-mediated gene transfer, thus providing the basis for future investigation of gene therapy as treatment for JAK3-deficient SCID.
Mots-clé
B-Lymphocytes/immunology, Blotting, Western, Cells, Cultured, Child, Cloning, Molecular, Consanguinity, Genes, Recessive, *Genetic Therapy, Genetic Vectors, Humans, Interleukin-2/pharmacology, Janus Kinase 3, Lymphocyte Activation/drug effects, Macromolecular Substances, Male, Protein-Tyrosine Kinases/biosynthesis/*deficiency/*genetics, Receptors, Interleukin/*genetics, Recombinant Proteins/biosynthesis, Retroviridae, Severe Combined Immunodeficiency/enzymology/*genetics/*therapy, Transfection, X Chromosome
Pubmed
Création de la notice
01/11/2017 10:29
Dernière modification de la notice
20/08/2019 15:12
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