TY - JOUR
T1 - IFN-Producing Killer Dendritic Cells Are Antigen-Presenting Cells Endowed with T-Cell Cross-Priming Capacity
AU - Pletneva, M.
AU - Fan, H.
AU - Park, J-J.
AU - Radojcic, V.
AU - Jie, C.
AU - Yu, Y.
AU - Chan, C.
AU - Redwood, Alec
AU - Pardoll, D.
AU - Housseau, F.
PY - 2009
Y1 - 2009
N2 - IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-γ, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II+ IKDC but not NK cross-present MHC class I–restricted antigens derived from MCMV-infected targets to CD8+ T cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen-presenting cell directly linking innate and adaptive immunity. [Cancer Res 2009;69(16):6607–14
AB - IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-γ, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II+ IKDC but not NK cross-present MHC class I–restricted antigens derived from MCMV-infected targets to CD8+ T cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen-presenting cell directly linking innate and adaptive immunity. [Cancer Res 2009;69(16):6607–14
U2 - 10.1158/0008-5472.CAN-09-0508
DO - 10.1158/0008-5472.CAN-09-0508
M3 - Article
C2 - 19679552
SN - 0008-5472
VL - 69
SP - 6607
EP - 6614
JO - Cancer Research
JF - Cancer Research
IS - 16
ER -
