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Dendritic Cell Produced IL‐12 Augments CD8+ T cell Activation through the Production of the Chemokines CCL1 and CCL17
Author(s) -
Henry Curtis James,
Grayson Jason M,
Ornelles David A,
Brzoza Kristina L,
Hiltbold Elizabeth M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.19
Subject(s) - ctl* , priming (agriculture) , dendritic cell , chemokine , immune system , immunology , cd8 , cytotoxic t cell , ccl17 , t cell , biology , in vitro , cxcl10 , biochemistry , botany , germination
Dendritic cells (DC) shape immune responses by producing cytokines such as Interleukin‐12 (IL‐12). IL‐12 is important in the clearance of the intracellular bacterial pathogen Listeria monocytogenes ( Lm ) and activates CD8+ T cells (CTL), which are required for sterilizing immunity. Our initial studies on the role of IL‐12 on CTL function determined that IL‐12p40 signals were transduced primarily during the first 48 hours of priming. However, these studies did not address the individual contributions of IL‐12 or IL‐23 nor how they affect the physical interactions of priming. To address these questions wild‐type, IL‐12p35−/−, or IL‐12p40−/− DC were infected with Lm and then used to prime CTL. IL‐12p40−/− mice immunized with p35−/− DC or p40−/− exhibited a reduced ability to clear Listeria compared to mice immunized with wild‐type DC. We found that CTL primed in vitro by p35−/− or p40−/− DC produced less IFN‐γ with the greatest reduction seen with the p40−/− DC, whereas proliferation was not affected. CTL primed in the absence of IL‐12 engaged in shorter duration interactions with DC which correlated with the absence of the chemokines CCL1 and CCL17. Neutralization of these chemokines resulted in decreased IFN‐γ production by CTL. Thus, CTL priming by DC is influenced more by the activity of IL‐12 than IL‐23 and in part through CCL1 and CCL17 whose production requires IL‐12. 1RO1AI057770‐01A1 and 1F31AI073245‐01A1