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

Authors

  • Ludmila Müller,

    1. Tübingen Ageing and Tumour Immunology Group (TATI), Section for Transplantation Immunology,
      University of Tübingen, and
    2. Second Department of Internal Medicine, University of Tübingen Medical School, Germany
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  • Carmelinda Provenzani,

    1. Tübingen Ageing and Tumour Immunology Group (TATI), Section for Transplantation Immunology,
      University of Tübingen, and
    2. Second Department of Internal Medicine, University of Tübingen Medical School, Germany
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  • Christoph Faul,

    1. Second Department of Internal Medicine, University of Tübingen Medical School, Germany
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  • Graham Pawelec

    1. Tübingen Ageing and Tumour Immunology Group (TATI), Section for Transplantation Immunology,
      University of Tübingen, and
    2. Second Department of Internal Medicine, University of Tübingen Medical School, Germany
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Ludmila Müller, Ph.D., Section for Transplantation Immunology, Second Department of Internal Medicine, University of Tübingen Medical School, Otfried-Müller Str.10, D-72076 Tübingen, Germany. E-mail: ludmila.mueller@med.uni-tuebingen.de

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-γ 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.

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