2000
DOI: 10.4049/jimmunol.164.6.2897
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TRAIL (Apo2 Ligand) and TWEAK (Apo3 Ligand) Mediate CD4+ T Cell Killing of Antigen-Presenting Macrophages

Abstract: The human marrow produces ∼1010 monocytes daily, and this production must be balanced by a similar rate of destruction. Monocytes/macrophages can undergo apoptosis after activating CD4+ T cells, suggesting one mechanism that may contribute to macrophage homeostasis. Previous reports indicate that Fas-Fas ligand interactions are the principle molecules mediating this response. However, D10, an Iak-restricted cloned Th2 line, will similarly induce apoptosis in Ag-presenting macrophages, and D10 cells lack Fas li… Show more

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Cited by 122 publications
(90 citation statements)
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“…Previous studies suggested that under certain conditions macrophages may be sensitive to TRAILmediated cell death (21,22). Therefore, we created a replication-defective adenovirus expressing human TRAIL (Ad-TRAIL) under the control of the CMV promoter-enhancer ( Figure 3A).…”
Section: Resultsmentioning
confidence: 99%
“…Previous studies suggested that under certain conditions macrophages may be sensitive to TRAILmediated cell death (21,22). Therefore, we created a replication-defective adenovirus expressing human TRAIL (Ad-TRAIL) under the control of the CMV promoter-enhancer ( Figure 3A).…”
Section: Resultsmentioning
confidence: 99%
“…Comparing the magnitude of the effect of these drugs on CD70 and LFA-1 is difficult, because LFA-1 is a 2-chain molecule and 5-azaC only affects CD11a (11), so the increase is limited by the amount of CD18 available. More recently, we reported that perforin expression is also abnormally increased in CD4ϩ T cells treated with DNA methylation inhibitors (9) and in CD4ϩ T cells from patients with active lupus, and it may contribute to disease pathogenesis by participating in autologous macrophage killing (8,9,14). The magnitude of the effect of 5-azaC on CD70 and perforin expression in CD4ϩ T cells is comparable (9).…”
Section: Discussionmentioning
confidence: 98%
“…Together, these studies suggest that T cell DNA hypomethylation may be fundamental to the pathogenesis of autoimmunity in the adoptive transfer model (4,5) and in humans with drug-induced and idiopathic lupus. While overexpression of LFA-1 and, perhaps, perforin is important to the disease process in the DNA hypomethylation model (7,13) and possibly in human lupus (8,11,14), the repertoire of genes that are affected is unknown, and other genes may also contribute to disease pathogenesis through mechanisms that promote antibody synthesis.…”
mentioning
confidence: 99%
“…TRAIL is a member of the TNF family and has a well-recognized role in mediating apoptosis not only of malignant cells, but also of monocytes, neutrophils, plasma cells, as well as normal and HIV-infected lymphocytes (3)(4)(5)(6)(7)(8)(9)(10). In humans, TRAIL interacts with five different receptors (11).…”
Section: T Cell Trail Promotes Murine Lupus By Sustaining Effectormentioning
confidence: 99%