Tumor-derived CD4(+)CD25(+) Regulatory T Cell Suppression of Dendritic Cell Function Involves TGF-beta and IL-10

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2006 Apr 14

PMID 16612596

Citations 90

Authors

Nicolas Larmonier

Marilyn Marron

Yi Zeng

Jessica Cantrell

Angela Romanoski

Marjan Sepassi

Sylvia Thompson

Xinchun Chen

Samita Andreansky

Emmanuel Katsanis

Affiliations

Soon will be listed here.

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-kappaB. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-alpha, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-beta and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor.

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