Viral dsRNA-activated human dendritic cells produce IL-27, which selectively promotes cytotoxicity in naive CD8+ T cells.
Viral recognition programs DCs to express Signal 3 molecules that promote the differentiation of effector CD8(+) T cells. Besides IL-12, another DC-derived IL-12 family member, IL-27, has been reported to contribute herein, but its specific role is not well understood. Here, we show that whereas IL-12 potently induces inflammatory cytokines (i.e., IFN-γ and TNF-α, but not IL-2), IL-27 excels in inducing proliferation and a cytotoxic profile (GrB, cytotoxicity of target cells) in human naïve CD8(+) T cells. Compared with bacterial cell-wall peptidoglycan, viral dsRNA-mimic poly (I:C) is superior in priming human BDCA1(+) peripheral blood DCs to produce IL-12 and IL-27, which promote inflammatory cytokines and a cytotoxic profile in differentiating CD8(+) T cells, respectively. These data support the concept that viral dsRNA-activated human DCs produce IL-27 to act as a specialized procytotoxic, antiviral cytokine in the development of effector CD8(+) T cells.
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
Rosa
R
de Groot
Astrid J
AJ
van Beelen
Ghaith
G
Bakdash
Esther W M
EW
Taanman-Kueter
Esther C
EC
de Jong
Martien L
ML
Kapsenberg
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007378:Interleukins; C464565:MYDGF protein, human; D012330:RNA, Double-Stranded; D012367:RNA, Viral