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Title: CD40 triggering of chronic lymphocytic leukemia B cells results in efficient alloantigen presentation and cytotoxic T lymphocyte induction by up-regulation of CD80 and CD86 costimulatory molecules
Authors: Van den Hove, L E ×
Van Gool, Stefaan
Vandenberghe, Peter
Bakkus, M
Thielemans, K
Boogaerts, Marc
Ceuppens, Jan #
Issue Date: Apr-1997
Series Title: Leukemia vol:11 issue:4 pages:572-80
Abstract: Freshly collected chronic lymphocytic leukemia B cells (B-CLL cells) are known to be inefficient at stimulating allogeneic T cells, and to lack significant expression of B7 (CD80 and CD86) costimulatory molecules. We investigated the potential of CD40 triggering to up-regulate the expression of adhesion and costimulatory molecules on B-CLL cells, and to enhance their immunogenicity towards allogeneic T cells. B-CLL cells cocultured with human CD40 ligand-expressing mouse fibroblasts rapidly up-regulated CD54 and CD58 adhesion molecules and B7-1 (CD80) and B7-2 (CD86) costimulatory molecules, and acquired a strong stimulatory capacity towards CD4+ as well as isolated CD8+ allogeneic T cells. Costimulation by both CD80 and CD86 proved critical for allogeneic T cell proliferation and CD25 and HLA-DR expression, since these were strongly inhibited by anti-CD80 or anti-CD86 monoclonal antibodies, and completely abrogated by CTLA4-Ig fusion protein, which blocks both CD80 and CD86. B7 costimulation also proved critical for restimulation of primed B-CLL-reactive T cells. Most importantly, priming of purified CD8+ T cells with CD40-triggered allogeneic B-CLL cells resulted in cytotoxic activity against the unstimulated B-CLL cells. These findings raise the possibility that CD40 triggering of B-CLL cells might be exploited in immunotherapeutic protocols.
ISSN: 0887-6924
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Laboratory of Clinical Immunology
Pediatric Hematology & Oncology Section (-)
Hematology Section (-)
Laboratory of Pediatric Immunology
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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