CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells

Taehoon Chun, Michael J. Page, Laurent Gapin, Jennifer L. Matsuda, Honglin Xu, Hanh Nguyen, Hyung Sik Kang, Aleksandar K. Stanic, Sebastian Joyce, Walter A. Koltun, Michael J. Chorney, Mitchell Kronenberg, Chyung Ru Wang

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112 Citations (Scopus)

Abstract

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 α-galactosylceramide (α-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 Vβ 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.

Original languageEnglish
Pages (from-to)907-918
Number of pages12
JournalJournal of Experimental Medicine
Volume197
Issue number7
DOIs
Publication statusPublished - 2003 Apr

Keywords

  • Avidity model
  • CD1
  • Lipid antigen
  • NKT cells
  • Negative selection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chun, T., Page, M. J., Gapin, L., Matsuda, J. L., Xu, H., Nguyen, H., Kang, H. S., Stanic, A. K., Joyce, S., Koltun, W. A., Chorney, M. J., Kronenberg, M., & Wang, C. R. (2003). CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells. Journal of Experimental Medicine, 197(7), 907-918. https://doi.org/10.1084/jem.20021366