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

Research output: Contribution to journalArticle

150 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume56
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Regulatory T-Lymphocytes
Interleukin-10
Dendritic Cells
Neoplasms
STAT3 Transcription Factor
Chemokine CCL5
Interleukin-12
Immunosuppressive Agents
Leukemia
Transcription Factors
Bone Marrow
T-Lymphocytes
Population

Keywords

  • Dendritic cells
  • Regulatory T cells
  • Tolerance
  • Tumor immunity

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10. / Larmonier, Nicolas; Marron, Marilyn; Zeng, Yi -; Cantrell, Jessica; Romanoski, Angela; Sepassi, Marjan; Thompson, Sylvia; Chen, Xinchun; Andreansky, Samita; Katsanis, Emmanuel.

In: Cancer Immunology, Immunotherapy, Vol. 56, No. 1, 01.2007, p. 48-59.

Research output: Contribution to journalArticle

Larmonier, Nicolas ; Marron, Marilyn ; Zeng, Yi - ; Cantrell, Jessica ; Romanoski, Angela ; Sepassi, Marjan ; Thompson, Sylvia ; Chen, Xinchun ; Andreansky, Samita ; Katsanis, Emmanuel. / Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10. In: Cancer Immunology, Immunotherapy. 2007 ; Vol. 56, No. 1. pp. 48-59.
@article{06211cfdeb0d43c6b9558f54d8ff100d,
title = "Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10",
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 = "Dendritic cells, Regulatory T cells, Tolerance, Tumor immunity",
author = "Nicolas Larmonier and Marilyn Marron and Zeng, {Yi -} and Jessica Cantrell and Angela Romanoski and Marjan Sepassi and Sylvia Thompson and Xinchun Chen and Samita Andreansky and Emmanuel Katsanis",
year = "2007",
month = "1",
doi = "10.1007/s00262-006-0160-8",
language = "English (US)",
volume = "56",
pages = "48--59",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "1",

}

TY - JOUR

T1 - Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10

AU - Larmonier, Nicolas

AU - Marron, Marilyn

AU - Zeng, Yi -

AU - Cantrell, Jessica

AU - Romanoski, Angela

AU - Sepassi, Marjan

AU - Thompson, Sylvia

AU - Chen, Xinchun

AU - Andreansky, Samita

AU - Katsanis, Emmanuel

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

KW - Dendritic cells

KW - Regulatory T cells

KW - Tolerance

KW - Tumor immunity

UR - http://www.scopus.com/inward/record.url?scp=33751371759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751371759&partnerID=8YFLogxK

U2 - 10.1007/s00262-006-0160-8

DO - 10.1007/s00262-006-0160-8

M3 - Article

C2 - 16612596

AN - SCOPUS:33751371759

VL - 56

SP - 48

EP - 59

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 1

ER -