https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25744 T), a single nucleotide polymorphism encoding substitution of arginine for tryptophan in PTPN22 (R620W), in 193 patients with PAD and 148 control subjects from an Australian cohort. We also performed a subgroup analysis according to the presence of autoimmunity and B-cell phenotypes. Results: C/T and T/T PTPN22 genotypes were more common in patients with PAD than in the matched control subjects (C/T, 18.1% vs 9.5%; T/T, 1.04% vs 0.6%). The T allele was associated with an increased risk of PAD relative to control subjects (odds ratio, 2.10; 95% CI, 1.11-4.00). The distribution of genotypes in control subjects was similar to those reported previously and did not deviate significantly from Hardy-Weinberg equilibrium. We found a strong association between the 1858T allele and PAD with coexistent autoimmune diseases. In patients with PAD and autoimmunity, 16 (43.2%) of 37 had at least one T allele of PTPN22 compared with 27 (17.3%) of 156 with the C/C genotype (P = .0014; odds ratio, 3.64; 95% CI, 1.68-7.88). We found no evidence that this effect was mediated by enrichment of CD21low B cells. Conclusion: The 1858T PTPN22 allele is strongly associated with autoimmunity in patients with PAD.]]> Sat 24 Mar 2018 07:30:54 AEDT ]]>