Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 33, Pages 11811-11816Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503366102
Keywords
antigen-presenting cell; innate immunity; natural killer T cell
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Funding
- NCI NIH HHS [P50 CA093683, P50 CA93683] Funding Source: Medline
- NIAID NIH HHS [R01 AI42955] Funding Source: Medline
- NIDDK NIH HHS [R01 DK066917] Funding Source: Medline
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Natural killer T cells (NKT cells) expressing a semiinvariant CD1d-reactive T cell receptor (invariant NKT, iNKT) can be rapidly activated by monocytes or immature dendritic cells (iDCs) bearing a CD1d-presented glycolipid antigen and can in turn stimulate these myeloid cells to mature and produce IL-12. Previous studies have shown that iNKT-produced IFN gamma and CD40 ligand contribute to this dendritic cell maturation. This study demonstrates that CD1d ligation alone, in the absence of iNKT, could rapidly (within 24 h) stimulate production of bioactive IL-12p70 by CD1d(+) human peripheral blood monocytes as well as iDCs. IFN gamma alone had no effect, but it markedly enhanced CD1d-stimulated IL-12 production. Monocyte differentiation, as assessed by CD40 and CD1a upregulation, was also accelerated by CD1d stimulation, consistent with this representing a physiological response. CD1d ligation on the human monocytic cell line THP-1 similarly specifically stimulated IL-12 production. Biochemical studies showed that IL-12 release correlated with rapid phosphorylation of I kappa B, a critical step in NF-kappa B activation. Selective NF-kappa B inhibition blocked this CD1d-stimulated IL-12 production. Finally, CD1d ligation could also enhance IL-12 production in the presence of suboptimal LPS or CD40 stimulation. These findings demonstrate an innate immune signaling function for CD1d and provide a mechanism for the rapid activation of monocytes and iDCs by CD1d-reactive T cells.
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