Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo

Mei Ling Chen, Mikaël J. Pittet, Leonid Gorelik, Richard A. Flavell, Ralph Weissleder, Harald Von Boehmer, Khashayarsha Khazaie

Research output: Contribution to journalArticle

535 Scopus citations

Abstract

Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor antigens (Ags). Yet, in most cases, such T cells fail to eradicate the tumor in vivo. Here, we investigated the interference of Ag-specif ic CD4+CD25+ regulatory T cells (Treg) with the tumor-specific CD8 T cell immune response in vivo, by monitoring the homing, expansion, and effector function of both subsets in draining and nondraining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-γ in the presence or absence of Ag-specific Treg. Nevertheless, these Treg abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-β because expression of a dominant-negative TGF-β receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity.

Original languageEnglish (US)
Pages (from-to)419-424
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number2
DOIs
StatePublished - Jan 11 2005

ASJC Scopus subject areas

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