TY - JOUR
T1 - Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo
AU - Chen, Mei Ling
AU - Pittet, Mikaël J.
AU - Gorelik, Leonid
AU - Flavell, Richard A.
AU - Weissleder, Ralph
AU - Von Boehmer, Harald
AU - Khazaie, Khashayarsha
PY - 2005/1/11
Y1 - 2005/1/11
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0408197102
DO - 10.1073/pnas.0408197102
M3 - Article
C2 - 15623559
AN - SCOPUS:12244285937
SN - 0027-8424
VL - 102
SP - 419
EP - 424
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -