Submitted May 9, 2008
Accepted February 14, 2009
Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells
Sabine Mumprecht, Christina Claus, Christian Schurch, Viktor Pavelic, Matthias S. Matter, and Adrian F. Ochsenbein*
Tumor Immunology, Department of Clinical Research, University of Berne, Berne, Switzerland
Institute for Medical Oncology, Inselspital, Berne, Switzerland
* Corresponding author; email: adrian.ochsenbein{at}insel.ch.
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease arising from a hematopoietic stem cell expressing the BCR/ABL fusion protein. Leukemic and dendritic cells (DCs) develop from the same transformed hematopoietic progenitors. How BCR/ABL interferes with the immunoregulatory function of DCs in vivo is unknown. We analyzed the function of BCR/ABL-expressing DCs in a retroviral-induced murine CML model using the glycoprotein of lymphocytic choriomeningitis virus (LCMV) as a model leukemia antigen. BCR/ABL-expressing DCs were found in bone marrow, thymus, spleen, lymph nodes and blood of CML mice. They were characterized by a low maturation status and induced only limited expansion of naive and memory cytotoxic T lymphocytes (CTLs). In addition, immunization with in vitro generated BCR/ABL-expressing DCs induced lower frequencies of specific CTLs than immunization with control DCs. BCR/ABL-expressing DCs preferentially homed to the thymus whereas only few BCR/ABL-expressing DCs reached the spleen. Our results indicate that BCR/ABL-expressing DCs do not efficiently induce CML-specific T cell responses due to low DC maturation and impaired homing to secondary lymphoid organs. In addition, BCR/ABL-expressing DCs in the thymus may contribute to CML-specific tolerance induction of specific CTLs.
