SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease

被引：44

作者：

Rivat, Christine ^{[1
]}

Booth, Claire ^{[1
]}

Alonso-Ferrero, Maria ^{[1
]}

Blundell, Michael ^{[1
]}

Sebire, Neil J. ^{[2
]}

Thrasher, Adrian J. ^{[1
]}

Gaspar, H. Bobby ^{[1
]}

机构：

[1] UCL Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London WC1N 1EH, England

[2] Great Ormond St Hosp Natl Hlth Serv Fdn Trust, Dept Histopathol, London, England

来源：

BLOOD | 2013年 / 121卷 / 07期

基金：

英国惠康基金;

关键词：

MICE DEFICIENT; THERAPY; CELLS; RESPONSES; IMMUNODEFICIENCY; ACTIVATION; SWITCH; SLAM;

D O I：

10.1182/blood-2012-07-445858

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)

引用

页码：1073 / 1076

页数：4

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