title: Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product.
abstract: SAP is an adaptor protein expressed in T cells and natural killer cells. It plays a critical role in immunity, as it is mutated in humans with X-linked lymphoproliferative syndrome (XLP), a fatal immunodeficiency characterized by an abnormal response to Epstein-Barr virus (EBV) infection. SAP interacts with the SLAM family receptors and promotes transduction signal events by these receptors through its capacity to recruit and activate the Src kinase FynT. Because it has been previously established that FynT is selectively required for the development of NKT cells, we examined NKT cells in SAP-deficient mice and in humans with XLP. In the absence of SAP, the development of NKT cells is severely impaired both in mice and in humans. These results imply that SAP is a potent regulator of NKT cell development. They also identify for the first time a defect in NKT cells associated with a human primary immunodeficiency, revealing a potential role of NKT cells in the immune response to EBV.
authors.affiliation: Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Unité INSERM 429.
authors.forename: Benoit
authors.initials: B
authors.lastname: Pasquier
authors.forename: Luo
authors.initials: L
authors.lastname: Yin
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Fondanèche
authors.forename: Francis
authors.initials: F
authors.lastname: Relouzat
authors.forename: Coralie
authors.initials: C
authors.lastname: Bloch-Queyrat
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambert
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint-Basile
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000494:pharmacology; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005699:Galactosylceramides; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C493154:alpha-galactosylceramide
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