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Several cytotoxic mechanisms have been attributed to T cells participating in β-cell death in type 1 diabetes. However, sensitivity of β-cells to these mechanisms in vitro and in vivo is likely to be different. Moreover, CD4⁺ and CD8⁺ T cells may use distinct mechanisms to cause β-cell demise that possibly involve activation of third-party cytotoxic cells. We used the transfer of genetically modified diabetogenic T cells into normal, mutant, and bone marrow chimeric recipients to test the contribution of major cytotoxic mechanisms in β-cell death. We found that 1) the killing of β-cells by CD4⁺ T cells required activation of the recipient's own cytotoxic cells via tumor necrosis factor-α (TNF-α); 2) CD8⁺ T-cell cytotoxic mechanisms destroying β-cells were limited to perforin and Fas ligand, as double knockouts of these molecules abrogated the ability of T cells to cause diabetes; and 3) individual CD8⁺ T-cell clones chose their cytotoxic weaponry by a yet unknown mechanism and destroyed their targets via either Fas-independent or Fas-dependent (~40% of clones) pathways. Fas-dependent destruction was assisted by TNF-α.
Pubmed ID: 22773667
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
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View all literature mentionsIrvine Scientific''s diversified products and services benefit both life science customers and medical customers. Irvine Scientific is proud of its past as an innovator of products that positively touch so many lives. Whether it is developing the highest quality embryo culture media to assist IVF procedures, supplying high quality media for diagnostics and research, or customizing media for cell therapy or bio-pharmaceutical production, Irvine Scientific''s primary goal is to provide the highest customer satisfaction. Irvine Scientific plans to build on this proud history and continue innovating to meet our customers???????????????????????? needs.
View all literature mentionsA web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.
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