Stephen I. Alexander

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Abnormalities in CD4(+)CD25(+)Foxp3(+) regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that(More)
T he science of kidney transplantation has progressed considerably in the past half-century largely because of an improved understanding of the role of the immune system in allograft rejection, the disentanglement of the molecular mechanisms underlying graft failure, and better management of immunosuppression. 1,2 Rejection has always been the major(More)
The effector cytokine interferon ␥ (IFN-␥) may play a role in T cell homeostasis. We have examined the requirement for IFN-␥ in one mechanism that regulates T cell expansion and survival , activation-induced cell death (AICD). CD4 ϩ T cells lacking IFN-␥ or the Stat1 transcription factor are resistant to AICD. IFN-␥ is required for the production of(More)
PURPOSE OF REVIEW Chronic allograft nephropathy is the major cause of late renal allograft loss. This disease is heterogeneous and the diagnosis is nonspecific, with both immune and nonimmune causes. Increasingly, we are able to recognize specific contributors to the disease. RECENT FINDINGS Further understanding of chronic allograft nephropathy comes(More)
Chronic proteinuric renal injury is a major cause of ESRD. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease whereby chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene that induces a regulatory T cell (Treg) phenotype. It was hypothesized that Foxp3-transduced Treg could protect(More)
Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse(More)
  • Min Hu, Geoff Y Zhang, +5 authors Stephen I Alexander
  • 2004
BACKGROUND Denys-Drash syndrome (DDS) is associated with mutations of the Wilms' tumour 1 (WT1) gene, and is characterized by pseudohermaphroditism, a progressive glomerulopathy, and the development of Wilms' tumour. More than 90% of patients with DDS who carry constitutional intragenic WT1 mutations are at high risk (90%) for the development of Wilms'(More)
Endothelial-mesenchymal transition (EndoMT) is a major source of myofibroblast formation in kidney fibrosis. Our previous study showed a profibrotic role for matrix metalloproteinase 9 (MMP-9) in kidney fibrosis via induction of epithelial-mesenchymal transition (EMT). Inhibition of MMP-9 activity reduced kidney fibrosis in murine unilateral ureteral(More)
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in(More)
BACKGROUND Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis. METHODS This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study. We prospectively collected(More)