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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3853-3858
CD40 activation does not protect chronic lymphocytic leukemia B
cells from apoptosis induced by cytotoxic T lymphocytes
Peter Chu,
William G. Wierda, and
Thomas J. Kipps
From the Biomedical Sciences Graduate Program and the Division of
Hematology/Oncology, University of California at San Diego School of
Medicine, La Jolla, CA.
Cytotoxic T lymphocytes (CTLs) can kill target cells by the
granule/exocytosis pathway or the Fas-mediated apoptosis pathway. The
sensitivity of chronic lymphocytic leukemia (CLL) B cells to
CTL-mediated apoptosis before and after CD40 activation was examined.
Resting or CD40-activated CLL cells were found to be equally sensitive
to class I-restricted CTL-mediated killing. Despite expressing
CD95, the CD40-activated CLL target cells were found to be
resistant to apoptosis induced by CH11, an IgM CD95 monoclonal antibody
(mAb). Consistent with this, inhibitors of caspases, which are involved
in the Fas-induced apoptotic pathway (eg, N-carbobenzoxy-Val-Ala-Asp
fluoromethyl ketone [z-VAD-fmk]), were unable to block destruction of
CLL target cells by CTL. In addition, preincubation of the effector T
cells with the anti-Fas ligand mAb NOK-2 failed to inhibit their
subsequent ability to kill CLL target cells. On the other hand, CTL
activity was blocked by inhibitors of the granule exocytosis
pathway such as ethylene-glyco-tetra-acetic acid or concanamycin A. These results indicate that CD40 activation does not impair the
sensitivity of CLL cells to Fas-independent CTL-mediated apoptosis.

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