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14 Invariant NKT Cells by Foreign Lipid Antigen Is Associated with Concurrent Dendritic Cell-Specific Self Recognition1
* Julia McFarlane Diabetes Research Centre, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Canada; and
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461
A burst release of cytokines by V
14 invariant NKT (iNKT) cells upon their TCR engagement critically regulates innate and adaptive immune responses. However, it remains unclear in vivo why iNKT cells respond efficiently to microbial or intracellular lipid Ags that are at low levels or that possess suboptimal antigenicity. We found that dendritic cells (DCs) potentiated iNKT cells to respond to a minimal amount of ligand -galactosylceramide (GalCer) through CD1d-dependent autoreactive responses that require endosomal processing and CD1d trafficking. The ability of potentiation of NKT cells was DC specific and did not depend on costimulatory signals and IL-12 production by DCs. However, DCs that failed to synthesize a major endogenous lipid Ag isoglobotrihexosylceramide were unable to potentiate NKT cells for efficient activation. Further analysis showed that differences in the level and pattern of endogenous lipid Ag presentation differentiate DCs and B cells for effective potentiation and subsequent activation of iNKT cells in the presence of an exogenous Ag. Thus, CD1d-dependent potentiation by DCs may be crucial for iNKT cell-mediated immunity against infectious agents.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Juvenile Diabetes Research Foundation International, Canadian Diabetes Association, and Julia McFarlane Diabetes Research Centre (to Y.Y.).
2 L.C., A.U., and S.C. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Yang Yang, Julia McFarlane Diabetes Research Centre, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Alberta, Canada T2N 4N1. E-mail address: yyang{at}ucalgary.ca
4 Abbreviations used in this paper: iNKT, invariant NKT; GalCer, -galactosylceramide; Baf, bafilomycin A1; CMA, concanamycin A; DC, dendritic cell; DGJ, deoxygalactonojirimycin; IB4, isolectin B4; iGb3, isoglobotrihexosylceramide; PDMP, threo-1-phenyl-2-decanoylamine-3-morpholine-propanol hydrochloride; PPMP, DL-thero-1-phenyl-2-palmitoylamino-3-morpholine-1-propanol; S-APC, splenic APC; Hex B, hexosaminidase B.
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