Natural killer T cells and X-linked lymphoproliferative syndrome.
OBJECTIVE
Recent progress in elucidating the physiopathology of X-linked lymphoproliferative syndrome (XLP) has raised novel and important issues regarding the biology of natural killer T cells. Here I will review this information and discuss the issues involved.


RESULTS
XLP is a rare inherited immunodeficiency characterized by a high susceptibility to severe infection by the Epstein-Barr virus. Mutations in the gene SH2D1A (or alternatively SAP) underlie 80% of familial XLP (XLP-1) cases. Recently the remaining 20% of familial XLP (XLP-2) cases were shown to harbor mutations in the gene XIAP (X-linked inhibitor of apoptosis protein). Both SAP and XIAP deficiencies are associated with a defect in the development and/or homeostasis of natural killer T cells.


CONCLUSIONS
It can be hypothesized that the susceptibility to Epstein-Barr virus in XLP might result from the defect of natural killer T cells. The role of these cells in viral infection is unclear, but several herpes viruses have developed strategies to escape natural killer T cells. The discovery that SAP and XIAP deficiency leads to a defect in natural killer T cells has also shed light on novel signaling pathways required for natural killer T cell development and/or homeostasis.
Latour
Sylvain
S
INSERM U768, Hôpital Necker-Enfants Malades, Paris, France. latour@necker.fr
D000818:Animals; D004195:Disease Models, Animal; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000276:immunology
D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human