/manager/Index ${session.getAttribute("locale")} 5 Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP /manager/Repository/uon:14363 + and SAP-cells. This represents the human equivalent of a mixed bone marrow chimera in mice. While memory CD8+ T cells specific for CMV and influenza were distributed across SAP+ and SAP- populations, EBV-specific cells were exclusively SAP+. The preferential recruitment of SAP+ cells by EBV reflected the tropism of EBV for B cells, and the requirement for SAP expression in CD8+ T cells for them to respond to Ag-presentation by B cells, but not other cell types. The inability of SAP- clones to respond to Ag-presenting B cells was overcome by blocking the SLAM receptors NTB-A and 2B4, while ectopic expression of NTB-A on fibroblasts inhibited cytotoxicity of SAP- CD8+ T cells, thereby demonstrating that SLAM receptors acquire inhibitory function in the absence of SAP. The innovative XLP carrier model allowed us to unravel the mechanisms underlying the unique susceptibility of XLP patients to EBV infection in the absence of a relevant animal model. We found that this reflected the nature of the Ag-presenting cell, rather than EBV itself. Our data also identified a pathological signalling pathway that could be targeted to treat patients with severe EBV infection. This system may allow the study of other human diseases where heterozygous gene expression from random X-chromosome inactivation can be exploited.]]> Wed 11 Apr 2018 13:37:53 AEST ]]> Expansion of somatically reverted memory CD8(+) T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus /manager/Repository/uon:23657 Wed 11 Apr 2018 13:34:30 AEST ]]>