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Oxidative damage role in fas-based cytotoxicity exerted by cytotoxic t-lymphocytes o target cells. Implication of mitochondria


Fas is a member of the TNF receptor family of proteins, that, when cross-linked by mAbs or its physiological ligand (FasL), induces apoptosis. Fas-mediated apoptosis is of physiological relevance in the regulation and function of the immune system. A biochemical mechanism for Fas-induced apoptosis, as well as for the apoptosis process itself, is unknown . Oxidative damage has been implicated in some forms of TNFmediated cytotoxicity. Mitochondrial respiration is the cellular process from which free radical could be more easily generated, and it is directly implicated in TNF-induced cell death of L929 cells. The implication of mitochondrial function in Fas-based cytotoxicity will be tested using mitochondrial DNA-depleted U937 and Jurkat cells, as both the promonocytic U937 and the T cell line Jurkat are sensitive to Fas-induced cytotoxicity. Fas-based cytotoxicity will be tested using effector T cells, that express the functional FasL on their surface upon activation, especially CD8+ CTL clones.

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Universidad de Zaragoza
S/n,gomez laguna
50013 Zaragoza

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