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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.

Type

Journal article

Journal

J Immunol

Publication Date

15/04/2004

Volume

172

Pages

4667 - 4671

Keywords

Animals, Antigen Presentation, Antigens, CD1, Antigens, CD1d, Cell Differentiation, Cytokines, Galactosylceramides, Hybridomas, Isoenzymes, Killer Cells, Natural, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, Protein Kinase C, Receptors, Antigen, T-Cell, alpha-beta, Signal Transduction