Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway
Porakishvili, N., Kardava, L., Jewell, A. P., Yong, K., Glennie, M. J., Akbar, A. and Lydyard, P. M. (2004) Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway. Haematologica, 89, (4), 435-443.
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Description/Abstract
BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) is a clonal expansion of CD5+B cells that accumulate due to their uncontrolled growth and resistance to apoptosis. We have previously shown that up to 50% of blood CD4+ T cells in B-CLL patients have a cytotoxicity-related CD28- CD57+ phenotype and high content of both granzyme B and perforin (PF). In this study we investigate the cytotoxic potential of these cells against autologous B-CLL cells. DESIGN-AND-METHODS: Blood CD4+ or CD8+ T cells were positively isolated from B-CLL patients and cultured under a range of conditions with autologous purified B-CLL cells and with bispecific [anti-CD3 x anti-CD19] antibodies. Apoptosis of labeled B-CLL cells was assessed using the change of mitochondrial membrane potential with the fluorescent dye DiOC6 and confirmed by annexin V binding. RESULTS: There was time- and dose-dependent killing of B-CLL cells by both CD8+ and CD4+ T cells and this ranged from 6.6 - 68.0% for CD4+ cells and 6.4 - 57.8% for CD8+ cells. Almost complete inhibition by concanamycin A suggests that CD4+ T cells like CD8+ T cells induced apoptosis through a perforin-mediated pathway, but not via Fas/FasL (as indicated by lack of blocking with brefeldin A), tumor necrosis factor alpha or TRAIL. INTERPRETATION-AND-CONCLUSIONS: This study shows that blood CD4+PF+ T cells enriched in B-CLL patients, are able to kill autologous B-CLL cells ex vivo, through bispecific antibodies via a perforin mediated mechanism.
| Item Type: | Article |
|---|---|
| ISSNs: | 1507-5077 (print) |
| Related URLs: | |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 26532 |
| Date Deposited: | 21 Apr 2006 |
| Last Modified: | 01 Jun 2011 04:12 |
| Contributors: | Porakishvili, N. (Author) Kardava, L. (Author) Jewell, A. P. (Author) Yong, K. (Author) Glennie, M. J. (Author) Akbar, A. (Author) Lydyard, P. M. (Author) |
| Date: | April 2004 |
| Status: | Published |
| Contact Email Address: | n_porakishvili@hotmail.com |
| URI: | http://eprints.soton.ac.uk/id/eprint/26532 |
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