Development of autologous cytotoxic CD4+ T clones in a human model of B-cell non-Hodgkin follicular lymphoma

Authors

  • Jian-Qing Mi,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
    2. Département de Cancérologie et d'Hématologie; Centre Hospitalier Universitaire Michallon
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  • Olivier Manches,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
    2. Laboratoires Immunocytologie et HLA; Département d'Immunologie Cellulaire; Etablissement Français du Sang, Site de Grenoble
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  • Jin Wang,

    1. Département de Cancérologie et d'Hématologie; Centre Hospitalier Universitaire Michallon
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  • Pascal Perron,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
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  • Sébastien Weisbuch,

    1. Laboratoire d'Immunochimie; Commissariat à l'Energie Atomique; Inserm U548; Université Joseph Fourier
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  • Patrice N. Marche,

    1. Laboratoire d'Immunochimie; Commissariat à l'Energie Atomique; Inserm U548; Université Joseph Fourier
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  • Jean-Charles Renversez,

    1. Département de Biologie Intégrée; Centre Hospitalier Universitaire Michallon, Grenoble, France
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  • Jean-Claude Bensa,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
    2. Laboratoires Immunocytologie et HLA; Département d'Immunologie Cellulaire; Etablissement Français du Sang, Site de Grenoble
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  • Jean-Jacques Sotto,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
    2. Département de Cancérologie et d'Hématologie; Centre Hospitalier Universitaire Michallon
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  • Jean-Yves Cahn,

    1. Département de Cancérologie et d'Hématologie; Centre Hospitalier Universitaire Michallon
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  • Dominique Leroux,

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
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  • Thierry Bonnefoix

    1. Institut National de la Santé et de la Recherche Médicale [Inserm E353, Lymphoma Research Group (Molecular Bases of Tumor Progression)]; Institut A. Bonniot; Université Joseph Fourier, La Tronche
    2. Département de Cancérologie et d'Hématologie; Centre Hospitalier Universitaire Michallon
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Jian-Qing Mi, MD, PhD, and Thierry Bonnefoix, MD, PhD, Département de Cancérologie et d'Hématologie, Centre Hospitalier Universitaire Michallon, 38043 G renoble, France.
E-mail: jian-qing.mi@ujf-grenoble.fr, mijg@yahoo.com or Thierry.Bonnefoix@ujf-grenoble.fr

Summary

Immunotherapy for cancer aims to generate cytotoxic cells that are capable of eradicating tumour cells. It has been well demonstrated that helper, non-cytotoxic CD4+ T cells are important for the induction and maintenance of anti-tumour immunity exerted by cytotoxic CD8+ T cells. In contrast, the existence of direct anti-tumour, effector cytotoxic CD4+ T cells remains elusive, mainly due to the paucity of reliable experimental data, especially in human B-cell non-Hodgkin lymphomas. This study developed an appropriate, autologous follicular B-cell non-Hodgkin follicular lymphoma model, including the in vitro establishment of a malignant, human leucocyte antigen class I (HLA-I) deficient B-cell line, and the generation of three autologous anti-tumour cytotoxic CD4+ T-cell clones originating from the peripheral blood of the same patient. These three clones were considered as tumour specific, because they were capable of killing the malignant, HLA-I-deficient B-cell line through a classical HLA-II restricted perforin-mediated pathway, but did not lyse the Epstein–Barr virus-infected autologous normal B lymphocytes. All three CD4+clones were T-cell receptor Vβ17-Dβ1-Jβ1·2 and exhibited an identical complementarity-determining region 3, suggesting the immunodominance of a single peptide antigen presented by tumour cells. Such lymphoma models would provide a useful tool for in vivo expansion and the adoptive transfer of selected CD4+ cytotoxic cells in immunotherapeutic strategies.

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