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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4128-4138. Prepublished online as a Blood First Edition Paper on September 8, 2008; DOI 10.1182/blood-2008-05-157529. This Article Full Text (PDF) Supplementary Figures and Videos All Versions of this Article: blood-2008-05-157529v1 112/10/4128    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Gumperz, J. E Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Gumperz, J. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 19, 2008 Accepted July 25, 2008 Natural killer T cell autoreactivity leads to a specialized activation state Xiaohua Wang, Xiuxu Chen, Lance Rodenkirch, William Simonson, Sarah Wernimont, Rachel M Ndonye, Natacha Veerapen, Darren Gibson, Amy R Howell, Gurdyal S Besra, Gavin F Painter, Anna Huttenlocher, and Jenny E Gumperz* Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States WM Keck Lab for Biological Imaging, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States Department of Chemistry, University of Connecticut, Storrs, CT, United States School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom Carbohydrate Chemistry Team, Industrial Research Ltd, Lower Hutt, New Zealand * Corresponding author; email: jegumperz{at}wisc.edu. NKT cells are innate-like T cells that recognize specific microbial antigens and also display autoreactivity to self antigens. The nature of NKT cell autoreactive activation remains poorly understood. We show here that the MAPK pathway is operative during human NKT cell autoreactive activation, but calcium signaling is severely impaired. This results in a response that is biased towards GM-CSF secretion because this cytokine requires ERK signaling but is not highly calcium dependent, while IFN, IL-4, and IL-2 production are minimal. Autoreactive activation was associated with reduced migration velocity but did not induce arrest, and thus NKT cells retained the ability to survey APCs. IL-12 and IL-18 stimulated autoreactively activated NKT cells to secrete IFN, and this was mediated by JAK-STAT dependant signaling without induction of calcium flux. This pathway did not require concurrent contact with CD1d+ APCs, but was strictly dependent on preceding autoreactive stimulation that induced ERK activation. In contrast, NKT cell responses to the glycolipid antigen -GalCer were dampened by prior autoreactive activation. These results show that NKT cell autoreactivity induces restricted cytokine secretion, and leads to altered basal activation that potentiates innate responsiveness to co-stimulatory cytokines while modulating sensitivity to foreign antigens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Hegde, E. Jankowska-Gan, D. A. Roenneburg, J. Torrealba, W. J. Burlingham, and J. E. Gumperz Human NKT cells promote monocyte differentiation into suppressive myeloid antigen-presenting cells J. Leukoc. Biol., October 1, 2009; 86(4): 757 - 768. [Abstract] [Full Text] [PDF]

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