Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion

doi:10.1073/pnas.0408288102

Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion

^*Department of Medical and Molecular Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010; ^†Department of Chemistry, Hunter College, 695 Park Avenue, New York, NY 10021; ^‡Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, 1081 BT, Amsterdam, The Netherlands; and The ^§Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016

Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved December 13, 2004 (received for review November 7, 2004)

Abstract

It has been shown that dendritic cells (DCs) are able to present glycolipids to natural killer (NK) T cells in vivo. However, the essential role of DCs, as well as the role of other cells in glycolipid presentation, is unknown. Here, we show that DCs are the crucial antigen-presenting cells (APCs) for splenic NK T cells, whereas Kupffer cells are the key APCs for hepatic NK T cells. Both cell types stimulate cytokine production by NK T cells within 2 h of glycolipid administration, but only DCs are involved in the systemic, downstream responses to glycolipid administration. More specifically, CD8α+ DCs produce IL-12 in response to glycolipid presentation, which stimulates secondary IFN-γ production by NK cells in different organs. Different APCs participate in glycolipid presentation to NK T cells in vivo but differ in their involvement in the overall glycolipid response.

Footnotes

↵ ¶ To whom correspondence should be addressed. E-mail: moriya.tsuji{at}med.nyu.edu.
Author contributions: J.S. and M.T. designed research; J.S. performed research; J.S. and M.T. analyzed data; J.S. and M.T. wrote the paper; and G.Y., R.W.F., and N.V.R. contributed new reagents/analytic tools.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: α-C-GalCer, α-C-galactosylceramide; α-GalCer, α-galactosylceramide; APC, antigen-presenting cell; DC, dendritic cell; DT, diphtheria toxin; DTR, DT receptor; ICCS, intracellular cytokine staining; NK, natural killer; Tg, transgenic; PE, phycoerythrin.