The dendritic cell-like functions of IFN-producing killer dendritic cells reside in the CD11b+ subset and are licensed by tumor cells.
IFN producing killer dendritic cells (IKDC) were originally defined as CD11c(int) B220(+)NK1.1(+) (or CD49b(+)) cells that exert a potent tumoricidal activity in animals lacking B, T, and conventional natural killer effectors. MHC class II expression on tumor infiltrating IKDC prompted us to investigate their putative antigen presenting function. Here, we show that tumor cells license IKDC to acquire the properties of antigen presenting cells, i.e., expression of MHC class II and costimulatory CD86 molecules. We show that the CD11b(+) subset of IKDC are able to prime naïve CD4(+) T cells and cross-prime naïve CD8(+) T lymphocytes. Licensing of IKDC by tumor cells was mandatory for the full differentiation of T cells into polarized effectors. IKDC could engulf and process soluble Ova protein in a CD206-dependent manner. Finally, we show that CD11b(+)IKDC is selectively endowed with CTLA4Ig-inhibitable antigen presenting capacities and that targeting this subset with the detoxified adenylate cyclase toxin of Bordetella pertussis fused to antigen resulted in efficient cross-presentation of antigen by IKDC to specific TCR transgenic CD8(+)T cells in vivo. Collectively, our data indicate that upon exposure to tumor cells, IKDC subserve DC-like functions.
Terme
Magali
M
Institut National de la Sante et de la Recherche Medicale, Villejuif, France.
Mignot
Grégoire
G
Ullrich
Evelyn
E
Bonmort
Mathieu
M
Minard-Colin
Véronique
V
Jacquet
Alexandra
A
Schultze
Joachim L
JL
Kroemer
Guido
G
Leclerc
Claude
C
Chaput
Nathalie
N
Zitvogel
Laurence
L
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology / Q000502:physiology; D051940:B7-2 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology
D051940:B7-2 Antigen; D039481:CD11b Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007372:Interferons