CD8α+ Dendritic Cells Induce Leukemia-Specific T cell Tolerance

Abstract Antigen presenting cells (APCs) are critical for the acquisition of tumor-derived antigens and the orchestration of anti-tumor T cell responses. Batf3-dependent CD8α+ and CD103+ dendritic cells (DCs) have been implicated as the critical APCs that initiate and maintain spontaneous CD8+ T cell priming against solid tumors. In contrast, little is known about the APCs that regulate immunity against malignancies of hematopoietic origin. Using a murine model of acute myeloid leukemia (AML) that induces T cell tolerance, we demonstrate that leukemia-derived antigens are exclusively acquired and cross-presented by CD8α+ DCs. In the steady state, CD8α+ DCs rapidly induce leukemia-specific T cell tolerance, which can be prevented upon the activation of these DCs. Together, our data reveal that the same DC lineage can imprint disparate T cell fates in mice with solid verses hematopoietic malignancies. In the context of solid tumors, Batf3-dependent DCs stimulate productive effector responses; however, in AML-bearing mice, CD8α+ DCs actively promote T cell tolerance.