Purpose of review: 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.
Recent findings: 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.
Summary: 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.