期刊
IMMUNITY
卷 32, 期 2, 页码 266-278出版社
CELL PRESS
DOI: 10.1016/j.immuni.2009.11.015
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资金
- Association pour la Recherche contre le Cancer (ARC)
- Ligue contre le Cancer (LNCC)
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- La Ligue Contre le Cancer
- Association de la Recherche Contre le Cancer
- Institut Curie
- Fondation Bettencourt-Schueller
- EC [DC-Thera NoLSBH-CT-2004-512074, LSHC-CT-2006-518234, ENCITE, Health-F5-2008-201842]
Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established oval-burnin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.
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