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Differential activation of the death receptor pathway in human target cells induced by cytotoxic T lymphocytes showing different kinetics of killing.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Vries, Jeltje F. De Borne, Peter A. Von Dem Luxemburg-Heijs, Simone A. P. Van Heemskerk, Mirjam H. M. Willemze, Roel Falkenburg, J. H. Frederik Barge, Renee M. Y. |
| Copyright Year | 2007 |
| Abstract | BACKGROUND AND OBJECTIVES Cytotoxic T lymphocytes (CTL) may use two effector mechanisms to kill their target cells: perforin (PFN) and granzyme B (GrB)-dependent granule-mediated cell death and death receptor-mediated cell death. Controversy exists whether, in addition to PFN/GrB-mediated apoptosis, death receptor-induced apoptosis contributes to the elimination of human tumor cells by CTL. DESIGN AND METHODS Since the two CTL-mediated effector mechanisms differ in time required to eliminate target cells, lysis of target cells was analyzed using CTL clones with slow and rapid kinetics of killing derived from a patient with chronic myeloid leukemia. To determine the involvement of the death receptor pathway, a retroviral construct encoding the antiapoptotic gene FLICE inhibitory protein (FLIP) was introduced into these target cells. RESULTS A CTL clone capable of killing 50% of the target cells within 2 hours of incubation primarily acted by release of PFN and GrB. In contrast, two CTL clones showing slower target cell killing kinetics partially used the death receptor pathway (approximately 30% inhibition by FLIP). INTERPRETATION AND CONCLUSIONS We demonstrated that the death receptor pathway contributes to T-cell-mediated cell death if not all target cells are destroyed by release of PFN and GrB. |
| Starting Page | 1 |
| Ending Page | 5 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://openaccess.leidenuniv.nl/bitstream/handle/1887/12980/04.pdf?sequence=9 |
| Alternate Webpage(s) | http://www.haematologica.org/content/haematol/92/12/1671.full.pdf |
| PubMed reference number | 18055991v1 |
| Volume Number | 92 |
| Issue Number | 12 |
| Journal | Haematologica |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Antiapoptotic Agent Apoptosis CD4 Positive T Lymphocytes CFLAR gene Cell Death Cessation of life Clone Cytotoxic T-Lymphocytes Excretory function Granzymes Helper-Inducer T-Lymphocyte Kinetics (discipline) Leukemia, B-Cell Myeloid Leukemia Neoplasms Patients Retroviridae autologous Epstein-Barr virus-specific cytotoxic T lymphocytes (cell) caspase-8 pathologic cytolysis perforin |
| Content Type | Text |
| Resource Type | Article |
