Cancer Immunology, Immunotherapy

, Volume 56, Issue 1, pp 48–59 | Cite as

Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10

  • Nicolas Larmonier
  • Marilyn Marron
  • Yi Zeng
  • Jessica Cantrell
  • Angela Romanoski
  • Marjan Sepassi
  • Sylvia Thompson
  • Xinchun Chen
  • Samita Andreansky
  • Emmanuel Katsanis
Original Article

Abstract

CD4+CD25+ regulatory T cells have been characterized as a critical population of immunosuppressive cells. They play a crucial role in cancer progression by inhibiting the effector function of CD4+ or CD8+ T lymphocytes. However, whether regulatory T lymphocytes that expand during tumor progression can modulate dendritic cell function is unclear. To address this issue, we have evaluated the inhibitory potential of CD4+CD25+ regulatory T cells from mice bearing a BCR–ABL+ leukemia on bone marrow-derived dendritic cells. We present data demonstrating that CD4+CD25+FoxP3+ regulatory T cells from tumor-bearing animals impede dendritic cell function by down-regulating the activation of the transcription factor NF-κB. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-α, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-β and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor.

Keywords

Tumor immunity Tolerance Dendritic cells Regulatory T cells 

Notes

Acknowledgments

The authors wish to thank Pawel Kiela for his helpful comments and Jennifer Uno for her help with real-time PCR. This work was supported in part by the NIH grant R01 CA104926 and the Tee Up for Tots Fund.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Nicolas Larmonier
    • 1
  • Marilyn Marron
    • 1
  • Yi Zeng
    • 1
  • Jessica Cantrell
    • 1
  • Angela Romanoski
    • 1
  • Marjan Sepassi
    • 1
  • Sylvia Thompson
    • 1
  • Xinchun Chen
    • 1
  • Samita Andreansky
    • 1
  • Emmanuel Katsanis
    • 1
  1. 1.Department of Pediatrics, Steele Children’s Research CenterUniversity of ArizonaTucsonUSA

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