Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B

J Immunol. 2004 Apr 15;172(8):4667-71. doi: 10.4049/jimmunol.172.8.4667.


The rapid and robust immunoregulatory cytokine response of Va14Ja18 natural T (iNKT) cells to glycolipid Ags determines their diverse functions. Unlike conventional T cells, iNKT lymphocyte ontogeny absolutely requires NF-kappa B signaling. However, the precise role of NF-kappa B in iNKT cell function and the identity of upstream signals that activate NF-kappa B in this T cell subset remain unknown. Using mice in which iNKT cell ontogeny has been rescued despite inhibition of NF-kappa B signaling, we demonstrate that iNKT cell function requires NF-kappa B in a lymphocyte-intrinsic manner. Furthermore, the ontogeny of functional iNKT cells requires signaling through protein kinase C theta, which is dispensable for conventional T lymphocyte development. The unique requirement of protein kinase C theta implies that signals emanating from the TCR activate NF-kappa B during iNKT cell development and function. Thus, we conclude that NF-kappa B signaling plays a crucial role at distinct levels of iNKT cell biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigens, CD1 / biosynthesis
  • Antigens, CD1d
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cytokines / biosynthesis
  • Galactosylceramides / immunology
  • Hybridomas
  • Isoenzymes / physiology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / deficiency
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • Protein Kinase C / physiology*
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*


  • Antigens, CD1
  • Antigens, CD1d
  • Cytokines
  • Galactosylceramides
  • Isoenzymes
  • NF-kappa B
  • Receptors, Antigen, T-Cell, alpha-beta
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta