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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3641-3647.
Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-06-2468.
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Submitted June 29, 2004
Accepted January 3, 2005
CpG stimulation of precursor B lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells towards a Th1 response
Gregor S Reid*, Kevin She, Luke Terrett, Michael R Food, Jacqueline D Trudeau, and Kirk R Schultz
Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada
* Corresponding author; email: grogreid{at}interchange.ubc.ca.
Immunostimulatory DNA containing unmethylated CpG induces the development of Th1 immune responses. The response of B cells to CpG stimulation involves increased proliferation, cytokine production and costimulatory molecule expression. Similar effects have been observed following CpG stimulation of a variety of malignant B cells. Pediatric precursor-B ALL cells express low levels of costimulatory molecules and are generally poor stimulators of T cell responses. In this study, we evaluated the impact of CpG stimulation on precursor B-ALL cell lines and pediatric patient-derived samples. The ability to respond to CpG oligodeoxynucleotides was determined by the level of TLR9 expression. In contrast to both non-leukemic B cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression. CpG stimulation of ALL blasts produced increased levels of IL-6, IL-8 and IL-10 but no detectable IL-12p70 and led to a skewing of allogeneic T cells, with enhanced IFN- production and reduced secretion of IL-5. These results demonstrate the functional relevance CpG stimulation of precursor B lineage ALL cells and provide a rational basis for study of these agents for use in treatment of this disease.

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