Defective homing and impaired induction of cytotoxic T cells by BCR/ABL-expressing dendritic cells

Blood. 2009 May 7;113(19):4681-9. doi: 10.1182/blood-2008-05-156471. Epub 2009 Feb 27.

Abstract

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 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 resulting from 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Dendritic Cells / physiology*
  • Disease Models, Animal
  • Flow Cytometry
  • Fusion Proteins, bcr-abl / metabolism*
  • Glycoproteins / physiology*
  • Immunization
  • Immunologic Memory / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Lymphocytic choriomeningitis virus / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Retroviridae / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • Whole-Body Irradiation

Substances

  • Glycoproteins
  • Fusion Proteins, bcr-abl