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.
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.
Van den Hove
L E
LE
Laboratory of Experimental Immunology, University Hospital Gasthuisberg, Catholic University of Leuven, Belgium.
Van Gool
S W
SW
Vandenberghe
P
P
Bakkus
M
M
Thielemans
K
K
Boogaerts
M A
MA
Ceuppens
J L
JL
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis*; D019013:CD40 Antigens / Q000032:analysis*; D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000032:analysis*; D007945:Leukemia, Lymphoid / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D019013:CD40 Antigens; D007519:Isoantigens