6533b7d0fe1ef96bd125ae72

RESEARCH PRODUCT

Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation

Stephan RouxArnaud ParcellierGuido KroemerBruno ChauffertPierre Emmanuel PuigFrançois MartinEric SolaryLaurence ZitvogelFrançois GhiringhelliElise Schmitt

subject

Regulatory T cellImmunologychemical and pharmacologic phenomenaBiologyT-Lymphocytes RegulatoryArticleMiceInterleukin 21Transforming Growth Factor betaCell Line TumorNeoplasmsmedicineAnimalsImmunology and AllergyCytotoxic T cellIL-2 receptorAntigen-presenting cellCell ProliferationDNA PrimersInterleukin 3Reverse Transcriptase Polymerase Chain ReactionCell DifferentiationForkhead Transcription FactorsRats Inbred Strainshemic and immune systemsDendritic CellsNatural killer T cellImmunohistochemistryMolecular biologyRatsCell biologymedicine.anatomical_structureBromodeoxyuridineInterleukin 12Receptors Transforming Growth Factor betaSignal Transduction

description

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.

https://doi.org/10.1084/jem.20050463