Chronic myelogenous leukemia maintains specific CD8(+) T cells through IL-7 signaling

Eur J Immunol. 2010 Oct;40(10):2720-30. doi: 10.1002/eji.201040404.

Abstract

Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease of hematopoietic stem cells. The disease progresses after several years from an initial chronic phase to a blast phase. Leukemia-specific T cells are regularly detected in CML patients and may be involved in the immunological control of the disease. Here, we analyzed the role of leukemia-specific CD8(+) T cells in CML disease control and the mechanism that maintains CD8(+) T-cell immunosurveillance in a retroviral-induced murine CML model. To study antigen-specific immune responses, the glycoprotein of the lymphocytic choriomeningitis virus was used as model leukemia antigen. Leukemia-specific CTL activity was detectable in vivo in CML mice and depletion of CD8(+) T cells rapidly led to disease progression. CML-specific CTL were characterized by the expression of the IL-7 receptor α-chain. In addition, leukemia cells produced IL-7 that was crucial for the maintenance of leukemia-specific CTL and for disease control. Therefore, CML cells maintain the specific CD8(+) T-cell-mediated immune control by IL-7 secretion. This results in prolonged control of disease and probably contributes to the characteristic chronic phase of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal
  • Flow Cytometry
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA / chemistry
  • RNA / genetics
  • Receptors, Interleukin-7 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Interleukin-7
  • Receptors, Interleukin-7
  • RNA