Cutting edge: the ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C theta and NF-kappa B.
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.
Stanic
Aleksandar K
AK
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Bezbradica
Jelena S
JS
Park
Jang-June
JJ
Van Kaer
Luc
L
Boothby
Mark R
MR
Joyce
Sebastian
S
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018949:Antigens, CD1 / Q000096:biosynthesis; D055610:Antigens, CD1d; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005699:Galactosylceramides / Q000276:immunology; D006825:Hybridomas; D007527:Isoenzymes / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D000074121:Protein Kinase C-theta; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; D007527:Isoenzymes; D016328:NF-kappa B; D016693:Receptors, Antigen, T-Cell, alpha-beta; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta