Enhanced Tumor Responses to Dendritic Cells in the Absence of CD8-Positive Cells

Abstract

Wild-type mice immunized with MART-1 melanoma Ag-engineered dendritic cells (DC) generate strong Ag-specific immunity that has an absolute requirement for both CD8+ and CD4+ T cells. DC administration to CD8α knockout mice displayed unexpectedly enhanced levels of protection to tumor challenge despite this deficiency in CD8+ T cells and the inability to mount MHC class I-restricted immune responses. This model has the following features: 1) antitumor protection is Ag independent; 2) had an absolute requirement for CD4+ and NK1.1+ cells; 3) CD4+ splenocytes are responsible for cytokine production; 4) lytic cells in microcytotoxicity assays express NK, but lack T cell markers (NK1.1+ αβTCR− CD3−); and 5) the lytic phenotype can be transferred to naive CD8α knockout mice by NK1.1+ splenocytes. Elucidation of the signaling events that activate these effective cytotoxic cells and the putative suppressive mechanisms in a wild-type environment may provide means to enhance the clinical activity of DC-based approaches.