期刊
BLOOD
卷 121, 期 7, 页码 1073-1076出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-07-445858
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资金
- Leukemia and Lymphoma Research Foundation
- Wellcome Trust
- European Commission [261387]
- Great Ormond Street Hospital Children's Charity
- Great Ormond Street Hospital Childrens Charity [V1266, V1223, V1242, V1259] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10001] Funding Source: researchfish
X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice. We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1. (Blood. 2013; 121(7): 1073-1076)
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