Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells

Authors

  • Weiyun Z. Ai,

    Corresponding author
    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
    2. Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA
    • Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305
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  • Jing-Zhou Hou,

    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
    2. Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
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  • Robert Zeiser,

    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
    2. Department of Hematology and Oncology, Albert-Ludwigs University Freiburg, Freiburg, Germany
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  • Debra Czerwinski,

    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
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  • Robert S. Negrin,

    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
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    • R. Levy and R. S. Negrin are co-senior authors.

  • Ronald Levy

    Corresponding author
    1. Divisions of Oncology, Hematology and Blood and Marrow Transplantation, Department of Medicine' Stanford University School of Medicine, Stanford, CA
    • Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305
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    • R. Levy and R. S. Negrin are co-senior authors.


Abstract

There has been accumulating evidence that CD4+CD25+ FoxP3 expressing regulatory T cells (Treg) are highly concentrated in tumors, thereby fostering an immune-privileged microenvironment. Some studies have shown that T-cell receptor (TCR) stimulation can convert conventional T cells into Treg. Follicular lymphoma (FL) B cells can enhance this Treg conversion. We investigated whether FL tumor B cells, as opposed to normal B cells, are unique in their ability to convert effector T cells into Treg. We found that tumor B cells alone, without artificial TCR stimulation, could induce conventional T cells to express FoxP3 and to acquire regulatory function. In contrast to their malignant counterpart, normal B cells did not induce Treg conversion. Treg conversion was independent of the T cell background, as T cells isolated from FL or normal peripheral blood were equally susceptible to being converted by tumor B cells. Our study provides evidence for a tumor-specific mechanism by which FL tumor cells promote immune escape through the induction of Treg. © 2008 Wiley-Liss, Inc.

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