Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product.
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.
Pasquier
Benoit
B
Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Unité INSERM 429.
Yin
Luo
L
Fondanèche
Marie-Claude
MC
Relouzat
Francis
F
Bloch-Queyrat
Coralie
C
Lambert
Nathalie
N
Fischer
Alain
A
de Saint-Basile
Geneviève
G
Latour
Sylvain
S
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
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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