Abstract

The CD11c^intB220⁺ NK1.1⁺ CD49⁺ subset of cells has recently been described as Interferon-producing killer dendritic cells (IKDCs), which share phenotypic and functional properties with both dendritic cells (DCs) and natural killer (NK) cells. We have previously demonstrated that IKDC within murine bone marrow derived DC preparations (BM-IKDC) are essential for the anti-tumour activity of unpulsed DCs.

Here we show that bone marrow-derived IKDC (BM-IKDC) migrate in vivo into tumours and thence to tumour draining lymph nodes, where they highly express MHC class II and costimulatory molecules. In vitro, freshly isolated BM-IKDC, FACS sorted to homogeneity, have no intrinsic antigen presentation function unless co-cultured with tumour target cells. On killing of target cells they can cross present antigens to stimulate nave or antigen primed CD8 T cells, and can also present antigen to antigen primed CD4 cells. In vivo, in mice lacking class I restricted APC function, robust proliferation of antigen specific T cells is achieved following adoptive transfer of BM-IKDC at an injection site distant to the tumour site.

Therefore, BM-IKDC are capable of potent antigen presentation but only after encountering antigen in the context of a viable target cell. This supports the concept of a murine dual function cell that is licensed by natural killer activity to develop antigen presentation function.