|
|
 Previous Article | Table of Contents | Next Article 
Efficient killing of chronic B-lymphocytic leukemia cells by
superantigen-directed T cells
A Wallgren, R Festin, C Gidlof, M Dohlsten, T Kalland and TH Totterman
Department of Clinical Immunology and Transfusion Medicine, University
Hospital, Uppsala, Sweden.
In vitro studies have indicated that chronic lymphocytic leukemia of B-
cell origin (B-CLL) is resistant to cytotoxic effector lymphocytes such as
natural killer and lymphokine activated killer (LAK) cells. We show here
that B-cell cells are sensitive to Staphylococcal enterotoxin (SE)
A-directed T-cell killing. Activation of the target cells by phorbol ester
(tetradecanoyl phorbol acetate, [TPA]) greatly enhances their sensitivity
to lysis. In SE-dependent cellular cytotoxicity (SDCC), members of the SE
superantigen family form a bridge between T cells and target cells
expressing major histocompatability complex class II molecules. Binding of
SEA to the T-cell-receptor V beta region induces a strong cytotoxic
capacity and cytokine production. Cells from 9 B-CLL patients were cultured
in the presence or absence of TPA and used as targets in a 4-hour SDCC
assay using an allogeneic T-cell line as effector. At an effector:target
cell ratio 30:1, 70% to 80% of TPA- induced B-CLL cells were killed. Even
at the effector:target ratio of 3:1, 47% +/- 6% of TPA-activated B-cell
cells were lysed compared with 13% +/- 2% of resting cells (P < .001). A
T-cell line established from a B-CLL patient killed autologous tumor cells
as efficiently as allogeneic effectors. SEA-directed T cells were far more
lytic to B-CLL cells compared with LAK cells or lectin
(phytohemagglutinin-directed T cells. Mechanisms of SDCC lysis were
investigated. Effector plus target cell supernatants contained high levels
of tumor necrosis factor (TNF)- alpha and interferon-gamma, but these
supernatants were not directly toxic to B-CLL cells in short term culture.
High concentrations of recombinant TNF-alpha or TNF-beta had no lytic
effect. Addition of neutralizing anti-TNF-alpha and anti-TNF-beta
antibodies into the SDCC assay did not inhibit SEA-directed T-cell killing.
TPA-activated B-CLL cells showed a 1.2- to 13-fold increased expression of
the adhesion molecules intercellular adhesion molecule-1 (ICAM-1),
lymphocyte function-associated antigen (LFA)-1, and LFA-3, whereas
expression of HLA class II molecules increased up to 5 times. The
expression of CD72, CD40, and BB-1/B7 increased 1.8 to 4.5 times. The role
of these surface molecules in SDCC was analyzed in blocking experiments
with monoclonal antibodies. Antibodies to ICAM-1, CD18, and HLA-DR
abolished the cytotoxicity, and a substantial reduction was seen with
antibody to CD72.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 82,
Issue 4,
pp. 1230-1238,
08/15/1993
Copyright © 1993 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J P Franklin, D P M Symmons, and A J Silman
Risk of lymphoma in patients with RA treated with anti-TNF{alpha} agents
Ann Rheum Dis,
May 1, 2005;
64(5):
657 - 658.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Batten, C. Fletcher, L. G. Ng, J. Groom, J. Wheway, Y. Laabi, X. Xin, P. Schneider, J. Tschopp, C. R. Mackay, et al.
TNF Deficiency Fails to Protect BAFF Transgenic Mice against Autoimmunity and Reveals a Predisposition to B Cell Lymphoma
J. Immunol.,
January 15, 2004;
172(2):
812 - 822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Balasa, A. La Cava, K. Van Gunst, L. Mocnik, D. Balakrishna, N. Nguyen, L. Tucker, and N. Sarvetnick
A Mechanism for IL-10-Mediated Diabetes in the Nonobese Diabetic (NOD) Mouse: ICAM-1 Deficiency Blocks Accelerated Diabetes
J. Immunol.,
December 15, 2000;
165(12):
7330 - 7337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Osorio, A. De Santiago, M. Aguilar-SantelisesHa, k. Mellstedt, and M. Jondal
CD6 Ligation Modulates the Bcl-2/Bax Ratio and Protects Chronic Lymphocytic Leukemia B Cells From Apoptosis Induced by Anti-IgM
Blood,
April 15, 1997;
89(8):
2833 - 2841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gidlof, M. Dohlsten, P. Lando, T. Kalland, C. Sundstrom, and T. H. Totterman
A Superantigen-Antibody Fusion Protein for T-Cell Immunotherapy of Human B-Lineage Malignancies
Blood,
March 15, 1997;
89(6):
2089 - 2097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
