Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency.

ABSTRACT: X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to an extreme, usually fatal increase in the number of lymphocytes upon infection with EBV. It is most commonly defined molecularly by loss of expression of SLAM-associated protein (SAP). Despite this, there is little understanding of how SAP deficiency causes lymphocytosis following EBV infection. Here we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by TCR restimulation, a process that normally constrains T cell expansion during immune responses. Expression of SAP and the SLAM family receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further, SAP/NTB-A signalin

SUBMITTER: Snow AL 

PROVIDER: S-EPMC2752081 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature