Comparison of five retrovirus vectors containing the human IL-2 receptor gamma chain gene for their ability to restore T and B lymphocytes in the X-linked severe combined immunodeficiency mouse model

Détails

ID Serval
serval:BIB_184D3D7CDC66
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Comparison of five retrovirus vectors containing the human IL-2 receptor gamma chain gene for their ability to restore T and B lymphocytes in the X-linked severe combined immunodeficiency mouse model
Périodique
Mol Ther
Auteur(s)
Aviles Mendoza G. J., Seidel N. E., Otsu M., Anderson S. M., Simon-Stoos K., Herrera A., Hoogstraten-Miller S., Malech H. L., Candotti F., Puck J. M., Bodine D. M.
ISSN
1525-0016 (Print)
ISSN-L
1525-0016
Statut éditorial
Publié
Date de publication
04/2001
Volume
3
Numéro
4
Pages
565-73
Langue
anglais
Notes
Aviles Mendoza, G J
Seidel, N E
Otsu, M
Anderson, S M
Simon-Stoos, K
Herrera, A
Hoogstraten-Miller, S
Malech, H L
Candotti, F
Puck, J M
Bodine, D M
eng
Comparative Study
Mol Ther. 2001 Apr;3(4):565-73.
Résumé
X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the IL-2 receptor gamma chain (IL2RG) gene, resulting in absent T lymphocytes and nonfunctional B lymphocytes. Recently T lymphocyte production and B lymphocyte function were restored in XSCID patients infused with autologous stem cells transduced with a retrovirus containing the human IL2RG cDNA. To optimize the expression of human IL2RG for future clinical trials, we compared five retroviral vectors expressing human IL2RG from different LTR enhancer-promoter elements in a mouse model. Northern and Southern blot analysis of hematopoietic tissues from repopulated mice revealed that the retroviral vector with the highest expression per copy number was MFG-S-hIL2RG, followed by MND-hIL2RG. All five vectors were capable of restoring lymphopoiesis in irradiated XSCID mice transplanted with transduced IL2RG-deficient hematopoietic stem cells. Transduction of IL2RG-deficient hematopoietic stem cells with all five vectors restored T lymphopoiesis in transplanted stem cell-deficient W/W(v) mouse recipients. However, only XSCID stem cells transduced with the MFG-S-hIL2RG vector generated B lymphocytes in W/W(v) mice. We conclude that the MFG-S-hIL2RG vector provides the best opportunity for in vivo selection and development of B and T lymphocytes for human XSCID gene therapy.
Mots-clé
3T3 Cells, Animals, B-Lymphocytes/*metabolism, Blotting, Northern, Blotting, Southern, DNA, Complementary/metabolism, Disease Models, Animal, Female, Flow Cytometry, *Genetic Linkage, Genetic Therapy/methods, *Genetic Vectors, Hematopoietic Stem Cells/metabolism, Humans, Lymphocytes/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, SCID, Models, Genetic, Mutation, Promoter Regions, Genetic, RNA, Messenger/metabolism, Receptors, Interleukin-2/*genetics, Retroviridae/*genetics/metabolism, Severe Combined Immunodeficiency/*therapy, T-Lymphocytes/*metabolism, Time Factors, Transduction, Genetic, X Chromosome/*genetics
Pubmed
Open Access
Oui
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
20/08/2019 13:48
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