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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 999-1006
Immunostimulatory CpG-oligonucleotides cause proliferation,
cytokine production, and an immunogenic phenotype in chronic
lymphocytic leukemia B cells
Thomas Decker,
Folker Schneller,
Tim Sparwasser,
Theresa Tretter,
Grayson B. Lipford,
Hermann Wagner, and
Christian Peschel
From the IIIrd Department of Medicine and the Institute
of Medical Microbiology and Hygiene, Technical University of Munich,
Munich, Germany.
Bacterial DNA and synthetic CpG-oligodeoxynucleotides (ODNs) derived
thereof have attracted attention because they activate cells of the
immune system in a sequence-dependent manner. Here we investigated the
potential of CpG-ODNs to cause proliferation, cytokine production, and
regulation of surface molecules in human B-chronic lymphocytic leukemia
(CLL) cells. CpG-ODN induced proliferation in both B-CLL cells and
normal B cells; however, only B-CLL cells increased proliferative
responses when CpG-ODN was added to co-cultures of CD40-ligand
transfected mouse fibroblasts (CD40LF) and B cells. Production of
interleukin-6 and tumor necrosis factor  was detectable at
borderline levels, using CpG-ODN as the only stimulus. In contrast, when CpG-ODN was added to co-cultures of B cells and CD40LF, a strong
increase in cytokine production occurred in B-CLL cells as well as in
normal B cells. The surface molecules CD40, CD58, CD80, CD86, CD54, and
MHC class I molecules were up-regulated in B-CLL cells, whereas CD95
expression was not influenced by CpG-ODN stimulation. The same pattern
of surface molecule regulation was observed in normal B cells, but
up-regulation of CD40 was significantly stronger in B-CLL cells.
Costimulation with CpG-ODN and CD40LF resulted in further up-regulation
of CD58, CD80, CD86, and MHC class I molecules. In contrast, CD95
expression induced by CD40-ligation was inhibited by CpG-ODN. CpG-ODN
activated B-CLL cells acquired a strong stimulatory capacity toward T
cells in allogeneic mixed lymphocyte reaction. This effect was
completely inhibited by a combination of anti-CD80 and anti-CD86
monoclonal antibody. Taken together, these findings suggest the
possible use of CpG-ODN for immunotherapeutic strategies in patients
with B-CLL.
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