Foxp3+ T Cells Induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes

Abstract

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. © 2010 Elsevier Inc. All rights reserved.