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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)
MDR1 P-glycoprotein (P-gp), the multidrug resistance-associated transmembrane transporter, is physiologically expressed by human peripheral immune cells, but its role in cell-mediated immunity remains poorly understood. Here, we demonstrate a novel role for P-gp in alloantigen-dependent human T cell activation. The pharmacologic P-gp inhibitor tamoxifen(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)
Both IL-4 and IL-10 are regulatory cytokines produced by Th2 cells that can down-regulate cell-mediated immune responses. The studies reported here examine the influence of various cytokines in the regulation of T cell IL-10 production. The results indicate that IL-10 gene expression by TCR transgenic Th2 cells is significantly up-regulated by IL-4 in the(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)
BACKGROUND Blockade of CD40-CD40 ligand (CD154) interactions protects against renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To investigate whether this protection relied on adaptive or cognate immunity, we tested the effect of CD40-CD154 blockade in severe combined immunodeficient (SCID) mice. METHODS SCID mice were divided into(More)
We have previously identified potential pathogenic T cells within glomeruli that use TCR encoding Vbeta5, Vbeta7, and Vbeta13 in combination with Jbeta2.6 in Heymann nephritis (HN), a rat autoimmune disease model of human membranous nephritis. Vaccination of Lewis rats with naked DNA encoding these pathogenic TCRs significantly protected against HN.(More)