The Journal of Experimental Medicine
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Published 7 April 2003. doi:10.1084/jem.20021366
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© Rockefeller University Press, 0022-1007/2003/4/907 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 907-918

CD1d-expressing Dendritic Cells but Not Thymic Epithelial Cells Can Mediate Negative Selection of NKT Cells

Taehoon Chun1,2, Michael J. Page3, Laurent Gapin4, Jennifer L. Matsuda4, Honglin Xu1,2, Hanh Nguyen1,2, Hyung-Sik Kang2, Aleksandar K. Stanic5, Sebastian Joyce5, Walter A. Koltun3, Michael J. Chorney3, Mitchell Kronenberg4 and Chyung-Ru Wang1,2

1 Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637
2 Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637
3 Department of Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033
4 La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
5 Department of Microbiology and Immunology, Vanderbilt University, School of Medicine, Nashville, TN 37232

Address correspondence to Chyung-Ru Wang, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 East 57th St., R412, Chicago, IL 60637-5420. Phone: 773-702-4725; Fax: 773-702-1576; E-mail: cwang{at}midway.uchicago.edu

Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid {alpha}-galactosylceramide ({alpha}-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vß usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen.

Key Words: NKT cells • CD1 • negative selection • avidity model • lipid antigen


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