Titre
Lymphoid development and function in X-linked severe combined immunodeficiency mice after stem cell gene therapy
Type
article
Institution
Externe
Périodique
Auteur(s)
Otsu, M.
Auteure/Auteur
Anderson, S. M.
Auteure/Auteur
Bodine, D. M.
Auteure/Auteur
Puck, J. M.
Auteure/Auteur
O'Shea, J. J.
Auteure/Auteur
Candotti, F.
Auteure/Auteur
Liens vers les personnes
ISSN
1525-0016
Statut éditorial
Publié
Date de publication
2000-02
Volume
1
Numéro
2
Première page
145
Dernière page/numéro d’article
53
Langue
anglais
Notes
Otsu, M
Anderson, S M
Bodine, D M
Puck, J M
O'Shea, J J
Candotti, F
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Mol Ther. 2000 Feb;1(2):145-53.
Anderson, S M
Bodine, D M
Puck, J M
O'Shea, J J
Candotti, F
eng
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Mol Ther. 2000 Feb;1(2):145-53.
Résumé
Mutations of the common gamma chain (gammac) of cytokine receptors cause X-linked severe combined immunodeficiency (XSCID), a candidate disease for gene therapy. Using an XSCID murine model, we have tested the feasibility of stem cell gene correction. XSCID bone marrow (BM) cells were transduced with a retroviral vector expressing the murine gammac (mgammac) and engrafted in irradiated XSCID animals. Transplanted mice developed mature B cells, naive T cells, and mature natural killer (NK) cells, all of which were virtually absent in untreated mice. The mgammac transgene was detected in all treated mice, and we could demonstrate mgammac expression in newly developed lymphocytes at both the RNA and protein level. In addition, treated mice showed T cell proliferation responses to mitogens and production of antigen-specific antibodies upon immunization. Four of seven treated animals showed a clear increase of the transgene positive cells, suggesting in vivo selective advantage for gene-corrected cells. Altogether, these results show that retroviral-mediated gene transfer can improve murine XSCID and suggest that similar strategies may prove beneficial in human clinical trials.
Sujets
PID Serval
serval:BIB_06597D93FA4D
PMID
Open Access
Oui
Date de création
2017-11-01T09:29:29.037Z
Date de création dans IRIS
2025-05-20T17:40:25Z