Migratory and antigen presentation functions of IFN-producing killer dendritic cells.
The CD11c(int) B220(+) NK1.1(+) CD49(+) subset of cells has recently been described as IFN-producing killer dendritic cells (IKDC), which share phenotypic and functional properties with both dendritic cells and natural killer cells. We have previously shown that IKDCs within murine bone marrow-derived DC preparations are essential for the antitumor activity of unpulsed DCs. Here we show that bone marrow-derived IKDCs (BM-IKDC) migrate in vivo into tumors and thence to tumor draining lymph nodes, where they highly express MHC class II and costimulatory molecules. In vitro, freshly isolated BM-IKDCs, fluorescence-activated cell sorted to homogeneity, have no intrinsic antigen presentation function unless cocultured with tumor target cells. On killing of target cells, they can cross-present antigens to stimulate antigen-primed CD8 T cells and can also present antigens to antigen-primed CD4 cells. In vivo, in mice lacking class I-restricted antigen-presenting cell function, robust proliferation of antigen-specific T cells is achieved after adoptive transfer of BM-IKDCs at an injection site distant to the tumor site. Therefore, BM-IKDCs are capable of cytotoxic killing of tumor targets and also of potent antigen presentation after encountering antigen in the context of a viable target cell.
Himoudi
Nourredine
N
University College London Institute of Child Health, Great Ormond Street Hospital, United Kingdom.
Yan
Mengyong
M
Bouma
Gerben
G
Morgenstern
Daniel
D
Wallace
Rebecca
R
Seddon
Ben
B
Buddle
Jo
J
Eddaoudi
Ayad
A
Howe
Steven J
SJ
Cooper
Nichola
N
Anderson
John
J
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D016654:Genes, RAG-1; D007372:Interferons / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D041681:NIH 3T3 Cells; D001613:beta 2-Microglobulin / Q000235:genetics
D001613:beta 2-Microglobulin; D007372:Interferons