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Aims: Vein grafts are frequently used conduits for arterial reconstruction in patients with cardiovascular disease. Unfortunately, vein graft disease (VGD) causes diminished patency rates. Innate immune system components are known to contribute to VGD. However, the role of T cells has yet to be established. The purpose of this study was to investigate the role of T cells and T cell activation pathways via the T cell receptor (TCR), co-stimulation and bystander effect in VGD. Methods and results: Here, we show upon vein graft surgery in mice depleted of CD4+ T cells or CD8+ T cells, that CD8+ T cells are locally activated and have a major protective role for vein graft patency. In presence of CD8+ T cells vein grafts appear patent while CD8+ T cell depletion results in occluded vein grafts with increases apoptosis. Importantly, the protective effect of CD8+ T cells in VGD development was TCR and co-stimulation independent. This was demonstrated in vein grafts of OT-I mice, CD70-/-, CD80/86-/-, and CD70/80/86-/- mice compared to C57BL/6 mice. Interestingly, cytokines including IL-15, IL-18, IL-33, and TNF are up-regulated in vein grafts. These cytokines are co-operatively capable to activate CD8+ T cells in a bystander-mediated fashion, in contrast to CD4+ T cells. Conclusions: T cells are modulators of VGD with a specific protective role of CD8+ T cells, which are locally activated in vein grafts. CD8+ T cells may protect against occlusive lesions by providing survival signals, and concert their protection independent of TCR and co-stimulation signaling.
Pubmed ID: 31263704
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Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
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