Foxp3+ T cells induce perforin-dependent dendritic cell death in tumor-draining lymph nodes.
Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (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.
Institut National de la Santé et de la Recherche Médicale U932, Immunité et Cancer, Institut Curie, F-75245 Paris Cedex 05, France.
Alexandre
A
Boissonnas
Alix
A
Scholer-Dahirel
Virginie
V
Simon-Blancal
Luigia
L
Pace
Fabien
F
Valet
Adrien
A
Kissenpfennig
Tim
T
Sparwasser
Bernard
B
Malissen
Luc
L
Fetler
Sebastian
S
Amigorena
D000818:Animals; D002448:Cell Adhesion; D016923:Cell Death; D045744:Cell Line, Tumor; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D054353:Perforin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D054353:Perforin