1. Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation
- Author
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Stephan Roux, Arnaud Parcellier, Guido Kroemer, Bruno Chauffert, Pierre Emmanuel Puig, François Martin, Eric Solary, Laurence Zitvogel, François Ghiringhelli, and Elise Schmitt
- Subjects
Regulatory T cell ,Immunology ,chemical and pharmacologic phenomena ,Biology ,T-Lymphocytes, Regulatory ,Article ,Mice ,Interleukin 21 ,Transforming Growth Factor beta ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Cell Proliferation ,DNA Primers ,Interleukin 3 ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Differentiation ,Forkhead Transcription Factors ,Rats, Inbred Strains ,hemic and immune systems ,Dendritic Cells ,Natural killer T cell ,Immunohistochemistry ,Molecular biology ,Rats ,Cell biology ,medicine.anatomical_structure ,Bromodeoxyuridine ,Interleukin 12 ,Receptors, Transforming Growth Factor beta ,Signal Transduction - Abstract
The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)–β receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-β–dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-β and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.
- Published
- 2005
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