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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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.
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|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)
|Contact Email Address:||firstname.lastname@example.org|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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