Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

A key goal of vaccine immunotherapy is the generation of long-term memory CM T cells capable of mediating immune surveillance We discovered a novel intercellular pathway governing the development of potent memory CD8+ T cell responses against cell-associated Ags that is mediated through cross-presentation by XCR1(+) dendritic cells (DCs). Generation of CD8(+) memory T cells against tumor cells pulsed with an invariant NKT cell ligand depended on cross-talk between XCR1(+) and plasmacytoid DCs that was regulated by IFN-alpha/IFN-alpha R signals. IFN-alpha production by plasmacytoid DCs was stimulated by an OX40 signal from the invariant NKT cells, as well as an HMGB1 signal from the dying tumor cells. These findings reveal a previously unknown pathway of intercellular collaboration for the generation of tumor-specific CD8(+) memory T cells that can be exploited for strategic vaccination in the setting of tumor immunotherapy.