https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35953 G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.]]> Tue 21 Jan 2020 09:52:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19772 Fri 29 May 2020 17:14:37 AEST ]]>