Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity

Patients with the X-linked lymphoproliferative disorder (XLPD) are unable t o control Epstein-Barr virus (EBV)-induced infections and lymphoproliferati on. This disease is caused by a deficit of SAP, an adapter protein involved in the signal transduction of several cell surface receptors of the CD2 su perfamily. One of these receptors, called 2B4, is expressed on NK cells, cy totoxic T cells and myeloid cells and activates NK cell cytotoxicity. Here we show that XLPD patients have a defect of 2B4 receptor-mediated NK cell c ytotoxicity. This defect may contribute to the pathogenesis of XLPD by redu cing NK cell lysis of EBV-infected B cells.