Recognition of chronic myelogenous leukaemia cells by autologous T lymphocytes primed in vitro against the patient's dendritic cells

Br J Haematol. 2001 Mar;112(3):740-8. doi: 10.1046/j.1365-2141.2001.02596.x.

Abstract

Defects in immune responses are common in patients with chronic myelogenous leukaemia (CML). However, using dendritic cells (DCs) to promote T-cell immunity in vitro may nonetheless elicit potent specific anti-tumour responses for use in immunotherapy. Here, we show that DCs generated from CML patients had a typical dendritic phenotype and were able to stimulate autologous T cells. Three primed T-cell lines were studied in more detail in one patient. They were stimulated by autologous CML cells, but not by normal non-leukaemic cells from the patient's HLA-identical sibling. This was blocked by HLA-DR-specific, but not HLA-DQ- or HLA-DP-specific antibodies. CML-stimulated cytokine secretion, including interferon-gamma and granulocyte macrophage-colony stimulating factor, suggested a Th1-type phenotype for these sensitized anti-leukaemic T cells. This study therefore shows that cells with a functional dendritic phenotype can be generated from the blood of CML patients and are potent inducers of T-cell responses to tumour cells. This approach allows sensitization of patients' T cells by their own particular tumour without the need to identify the exact leukaemia antigens involved, and may find application in immunotherapy of CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division
  • Cell Line
  • Cells, Cultured
  • Clone Cells
  • Dendritic Cells / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Interleukin-4 / pharmacology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Lymphocyte Activation
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor