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

Stanic AK, Bezbradica JS, Park JJ, Van Kaer L, Boothby MR, Joyce S
J Immunol. 2004 172 (8): 4667-71

PMID: 15067039 · 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.

MeSH Terms (19)

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 Protein Kinase C-theta Receptors, Antigen, T-Cell, alpha-beta Signal Transduction

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