CD40 engagement stimulates IL-12 p70 production by human microglial cells: basis for Th1 polarization in the CNS.
The APC-derived cytokine interleukin (IL)-12 polarizes CD4 T cells towards the pro-inflammatory Th1 phenotype and has been shown to be crucial for the development of EAE in rodents. In this study we demonstrate that production of IL-12 by human adult CNS-derived microglial cells can be triggered by cell contact with activated T cells. Microglial activation and IL-12 production can be blocked by anti-CD154 mAbs. IL-12 production could also be induced by direct engagement of CD40 on microglia using a CD40 agonist. IL-12 secretion by microglia is significantly reduced by TNF and IFN-gamma antagonists showing that the IL-12 production is subject to regulation by auto- and paracrine stimuli.
Becher
B
B
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03576, USA. burkhard.becher@dartmouth.edu
Blain
M
M
Antel
J P
JP
D001921:Brain / Q000166:cytology / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand; D016764:Cell Polarity / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma