|
|
Blood, 15 April 2005, Vol. 105, No. 8, pp. 3193-3198.
Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2003-10-3684.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells
Frank Dicker,
Arnon P. Kater,
Tetsuya Fukuda, and
Thomas J. Kipps
From the John and Rebecca Moores Cancer Center, University of California at San Diego, La Jolla, CA; and the Department of Hematology and Experimental Immunology, Academic Medical Center, University of Amsterdam, The Netherlands.
Chronic lymphocytic leukemia (CLL) B cells become sensitive to Fas (CD95)–mediated apoptosis 3 to 5 days after CD40 ligation. However, CD4+ cytotoxic T lymphocytes (CTLs) can kill CLL B cells via a Fas-ligand (CD178)–dependent process within 24 hours after CD40 cross-linking, when ligation of CD95 alone is insufficient to induce apoptosis. In addition to CD95, CD40-activated CLL cells also express DR5, a receptor for tumor-necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) that is expressed by CD4+ CTL. In addition, CD40 ligation in vitro and in vivo induces CLL cells to express the proapoptotic protein, BH3 interacting domain death agonist (Bid), which can facilitate crosstalk between mitochondrial-dependent, apoptosis-inducing pathways and death receptors, such as death receptor 5 (DR5). To evaluate whether ligation of CD95 and/or DR5 can induce apoptosis of CD40-activated CLL cells, we generated artificial cytotoxic effector cells that express both human TRAIL and CD178 (Chinese hamster ovary [CHO]–CD178/TRAIL) or only TRAIL (CHO-TRAIL) or CD178 (CHO-CD178). CHO-CD178/TRAIL cells were significantly more effective in killing CD40-activated CLL cells than either CHO-TRAIL or CHO-CD178 and, unlike the latter, could kill CLL cells 24 hours after CD40 ligation. We conclude that CD40 ligation induces CLL cells to express the proapoptotic molecule Bid and the death receptors CD95 and DR5, the latter of which can act synergistically to induce caspase-dependent apoptosis of CD40-activated CLL B cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Troeger, L. Glouchkova, B. Ackermann, G. Escherich, R. Meisel, H. Hanenberg, M. L. den Boer, R. Pieters, G. E. Janka-Schaub, U. Goebel, et al.
High expression of CD40 on B-cell precursor acute lymphoblastic leukemia blasts is an independent risk factor associated with improved survival and enhanced capacity to up-regulate the death receptor CD95
Blood,
August 15, 2008;
112(4):
1028 - 1034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Secchiero, E. Melloni, M. Tiribelli, A. Gonelli, and G. Zauli
Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells
J. Leukoc. Biol.,
February 1, 2008;
83(2):
434 - 437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. G. Wierda
Treatments for Patients with Chronic Lymphocytic Leukemia
ASCO Educational Book,
January 1, 2008;
2008(1):
297 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. de Totero, R. Meazza, S. Zupo, G. Cutrona, S. Matis, M. Colombo, E. Balleari, I. Pierri, M. Fabbi, M. Capaia, et al.
Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells
Blood,
May 1, 2006;
107(9):
3708 - 3715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Gowda, X. B. Zhao, C. Cheney, N. Mehter, G. Lozanski, T. S. Lin, S. Guster, J. G. Drachman, N. Muthusamy, and J. C. Byrd
Humanized Anti CD-40 Antibody SGN-40 Effectively Induces Cytotoxicity Against Chronic Lymphocytic Leukemia (CLL) Cells through Antibody Mediated Cytotoxicity and Demonstrates Modest Biologic Evidence of CD40 Activation.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
2966 - 2966.
[Abstract]
|
|
|
|
|
|
|
W. G. Wierda, T. J. Kipps, and M. J. Keating
Novel Immune-Based Treatment Strategies for Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
September 10, 2005;
23(26):
6325 - 6332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Kater, F. Dicker, M. Mangiola, K. Welsh, R. Houghten, J. Ostresh, A. Nefzi, J. C. Reed, C. Pinilla, and T. J. Kipps
Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis
Blood,
September 1, 2005;
106(5):
1742 - 1748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
