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Cutting Edge: The Ontogeny and Function of Va14Ja18 Natural T Lymphocytes Require Signal Processing by Protein Kinase C and NF-B¹

Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232

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-B signaling. However, the precise role of NF-B in iNKT cell function and the identity of upstream signals that activate NF-B in this T cell subset remain unknown. Using mice in which iNKT cell ontogeny has been rescued despite inhibition of NF-B signaling, we demonstrate that iNKT cell function requires NF-B in a lymphocyte-intrinsic manner. Furthermore, the ontogeny of functional iNKT cells requires signaling through protein kinase C, which is dispensable for conventional T lymphocyte development. The unique requirement of protein kinase C implies that signals emanating from the TCR activate NF-B during iNKT cell development and function. Thus, we conclude that NF-B signaling plays a crucial role at distinct levels of iNKT cell biology.

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