Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis

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Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis

Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune CD8(+) T cells from mice deficient in perf, gzmA and/or gzmB, and the Fas-resistant EL4.F15 tumor target cell, we show that (a) CTL from g...

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Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia.

Recent studies demonstrated that autophagy is an important regulator of innate immune response. However, the mechanism by which autophagy regulates natural killer (NK) cell-mediated antitumor immune responses remains elusive. Here, we demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated lysis in vitro via the activation of autophagy. This impairment was not related ...

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Granule-mediated Killing: Pathways for Granzyme B–initiated Apoptosis

We report that the serine protease granzyme B (GrB), which is crucial for granule-mediated cell killing, initiates apoptosis in target cells by first maturing caspase-10. In addition, GrB has a limited capacity to mature other caspases and to cause cell death independently of the caspases. Compared with other members, GrB in vitro most efficiently processes caspase-7 and -10. In a human cell mo...

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Kinetics of Primary and Memory Cytotoxic T Lymphocyte Responses to Herpes Simplex Virus 1 Infection: Granzyme B Mediated CTL Activity

Background: Herpes simplex virus type 1 is one of the most common viruses among human population. Studies demonstrate the essential role of cell mediated immunity, especially CD8+ T cells, in prevention and clearance of HSV1. Objective: It is of great importance to improve our knowledge about the kinetics of CTL responses to primary and secondary HSV-1 infection. Methods: Using a sensitive tech...

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Inhibition of CPP32-like proteases prevents granzyme B- and Fas-, but not granzyme A-based cytotoxicity exerted by CTL clones.

The perforin-facilitated entry of granzymes in target cells is a major mechanism used by CTL to induce cell death. It has been reported that granzyme B can cleave and activate the apoptotic cysteine protease p32 (CPP32)/Yama and its homologues in vitro. However, the mechanism for granzyme-based cytolysis exerted by intact CTL remains unclear. In the present work, we have used anti-CD3 mAb-redir...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2004

ISSN: 1540-8140,0021-9525

DOI: 10.1083/jcb.200406115